Carbonylane dendrones functionalized with fatty acids: formation of micelles and uses (Machine-trans

专利摘要:
The present invention relates to the formation of dendrons of carbosilane structure, which preferably have anionic or cationic groups at their periphery and, at the focal point, fatty acids or derivatives thereof. There are also dendrimers formed by two different units (Janus type), which consist of a fragment derived from the previous dendrons and another derivative of dendrons that have fatty acids or derivatives thereof in the periphery. The present invention also relates to the formation of micelles from the above compounds. In addition, the invention comprises the uses of said compounds in biomedicine. (Machine-translation by Google Translate, not legally binding)
公开号:ES2657282A1
申请号:ES201600726
申请日:2016-09-02
公开日:2018-03-02
发明作者:Francisco Javier De La Mata De La Mata；Rafael Gómez Ramírez；Javier Sánchez-Nieves Fernández；Gabriel MENCIA BERLINCHES；Jesús CANO SIERRA；José Luis COPA PATIÑO；Juan Soliveri De Carranza；Jorge PÉREZ SERRANO；Mercedes VALIENTE MARTÍNEZ；Carlos Emilio GUTIÉRREZ ULLOA；M. Ángeles MUÑOZ FERNÁNDEZ；José Luis Jiménez Fuentes；Carlos GUERRERO BELTRÁN；Daniel SEPÚLVEDA CRESPO；Rafael CEÑA DÍEZ
申请人:Universidad de Alcala de Henares UAH；Fundacion para la Investigacion Biomedica del Hospital Gregorio Marañon；
IPC主号:

专利说明:

 5 CARBOSILAN DENDRONS FUNCTIONED WITH FATTY ACIDS: TRAINING OF MICELS AND USES SECTOR OF THE TECHNIQUE The present invention relates to the formation of dendrons of carbosilane structure which preferably have anionic or cationic groups on their periphery and fatty acids or derivatives of focal point these.  There are also dendrimers formed by two different units (Janus type), which consist of a fragment derived from the 10 previous dendrons and another derived from dendrons that have fatty acids or derivatives derived from them.  The present invention also relates to the formation of micelles from the above compounds.  In addition, the invention comprises the uses of said compounds in biomedicine.  15 STATE OF THE TECHNIQUE Despite the progress of medicine in the search for solutions for the improvement of human health, an important barrier continues to hinder the full development and evaluation of these solutions, such as the transport and release of new drugs in the 20 conditions suitable for optimal use.  In particular, this problem is manifested mainly in the case of low solubility drugs, peptides and nucleic acids, and in diseases such as cancer.  The low solubility of some drugs entails the need to use concentrations that are too high for their action, with the consequent increase in adverse effects.  In addition, the selectivity observed in some drugs in the treatment of different cancers between healthy and tumor cells ceases to make sense if the drug is not able to reach the affected areas at the appropriate concentrations.  Another drawback of many drugs is their low molecular weight, which significantly decreases their circulation time.  On the other hand, the use of nucleic acids requires avoiding their easy degradation in the bloodstream.  To try to overcome these difficulties, different systems have been developed that are capable of facilitating the transport of the aforementioned derivatives, 35 favoring their solubility, increasing their stability and even acting as 2transporters to the areas of interest.  The vast majority of these systems have a nanoscopic size, and among them are dendritic molecules and micelles.  The conjugation with these systems is done either by covalent bonding, or by electrostatic interactions, being able to modify its presentation in 5 biological means to reduce its inconveniences.  Micelles consist of a supramolecular arrangement of compounds that have a clearly delimited hydrophobic and hydrophilic part.  Exposure of these systems in aqueous medium, for example, would give rise to these micelles that would present the 10 hydrophilic groups towards the outside of the micelle.  This arrangement occurs from a certain concentration, called the critical micellar concentration (CMC).  As a consequence of this construction, the micelles are able to act as transporters of hydrophobic drugs by internalizing them in their internal structure, while their water-soluble part allows their vehiculization precisely in the bloodstream (M.  Talelli, M.  Barz, et al.  Nano Today 2015, 10, 93).  In this sense, different types of micelles have been studied with mainly anticancer drugs (E.  Pérez-Herrero, A.  Fernández-Medarde Eur.  J.  Pharm  Biopharm  2015, 93, 52).  20 This encapsulation capacity has also been used for the transport of peptides and nucleic acids (O Akagi, M Oba, et al.  Gene Therapy, 2007, 14, 1029).  To this end, compounds have been used in some cases that have positive charges that interact with them together with hydrophilic units that would facilitate the encapsulation of the nucleic acid in the micellar interior.  25 Dendritic molecules, dendrimers and dendrons, are hyperbranched molecules of arborescent construction, of a well-defined size and three-dimensional structure and that have uniform chemical properties due in part to their low polydispersity as a consequence of their controlled synthesis (G.  R.  Newkome, C.  Or Shreiner.  Polymer 30 2008, 49, 1; J.  M.  J.  Fréchet, O.  TO.  Tomalia  Dendrimers and Other Dendritic Polymers VCH, Weinheim 2002).  The dendrimers have a spherical molecular topology, mainly in older generations, while the dendron topology is cone or wedge.  In both cases, there is a surface that contains the active groups of these molecules.  In addition, in the case of dendrons, these present a 3additional position called focal point, which can be used to introduce a new active function or as an anchor to other systems.  Dendrimers and dendrons themselves can have biological activity, thus acting as for example as antibacterial, antiviral or antiprionic agents.  They can also act as transport agents for nucleic acids or drugs.  This activity depends mainly on the peripheral functions, and seems to be related to the multivalence that dendrimers have, which allows the presence of a large number of functionalities on the same molecule, and its nanoscopic size.  The dendritic molecules 10 described in the literature and potentially useful as antiviral agents have on their periphery some of the following functions: carbohydrates, peptides and anions (J.  M.  J.  Fréchet, D.  TO.  Tomalia  Dendrimers and Other Dendritie Polymers VCH, Weinheim 2002).  On the other hand, dendritic molecules with cationic groups are used as transporters of nucleic acids in therapies against HIV, cancer, etc., through the formation of nanoconjugates called dendriplexes (S.  Svenson, D.  TO.  Tomalia  Adv.  Drug  Deliv.  Rev.  2005, 2106); or they have antimicrobial properties (Ana M.  Carmona-Ribeiro, Letícia Dias de Melo-Carrasco.  Int.  J.  Mol.  Yeah  2013, 14,9906).  With regard to the transport of drugs, the nature of the latter (cationic or anionic) determines in some way the type of dendrimer to be used when an electrostatic interaction is sought.  However, if a covalent binding of the drug is performed, the presence of additional cationic or anionic groups will serve to favor the solubility of the drug or generate synergies with the activity of the ionic groups of the dendritic molecule.  Another aspect to consider in the formation of dendritic molecules is their internal structure.  Different dendritic skeletons have been described, among which is the carbosilane skeleton, characterized by the presence of very stable C-C and Si-C bonds, of low polarity.  With this type of skeleton, carbosilane dendritic molecules of both cationic and anionic nature have been prepared (W02011 / 101520 A2).  The former have shown their ability to interact with oligonucleotides or 35 small interfering RNAs and transport them to the interior of the cells, so 4they can be considered as non-viral vectors for the transfection of nucleic material into several types of cell lines in gene therapy processes (N.  Weber, P.  Ortega, et al.  J.  Control.  Released  2008, 132, 55).  These systems are even capable of overcoming the blood brain barrier (M.  J.  Serramía, S.  Álvarez, et al.  J.  Control.  Released  5 2015, 200, 60).  Also, cationic carbosilane dendrimers and dendrons have antimicrobial activity both against Gram positive bacteria and against Gram negative bacteria (E.  Fuentes, J.  Sánchez-Nieves, et al.  RSC Adv. , 2016, 6, 7022).  In addition, cationic carbosilane dendritic molecules did not generate resistance in the bacteria treated with them and maintain their activity against resistant bacteria.  10 15 As for anionic carbosilane systems, the presence of carboxylate, sulphonate and sulfate groups in them has given them an antiviral activity against HIV.  The importance of its antiviral ability is because it prevents infection of epithelial cells and also reduces infection in already infected cells.  The synthetic process of carbosilane systems uses various approaches.  To obtain cationic systems, allylamine hydrosilylation reactions have been used (eg.  C3HsNH2, C3HsNMe2) with dendrimers and dendrons with Si-H terminal links and subsequent quaternization, for example with HCI and Mel (P.  Ortega, B.  M.  Cobaleda, et al.  Org.  20 Biomo /.  Chem  2011, 9, 5238).  Dendrimer alcoholysis reactions with Si-CI bonds have also been used, although in this case unstable dendrimers are obtained in the presence of water (J.  F.  Bermejo, Paula Ortega, et al.  Chem  Eur.  J.  2007, 13,483).  Finally, the thiol-ene addition of thiols that support ammonium groups, which allow to obtain cationic dendrimers and dendrons more simply (E.) has been more recently documented.  Fuentes-Paniagua, J.  M.  Hernández-Ros, et al.  Rsc Adv.  2014, 4, 1256).  On the other hand, to obtain anionic carbosilane dendrimers, Michael-type additions of methyl acrylate or vinyl sulphonate have been made on systems with terminal functions -NH2 (B.  Rasines, J.  Sánchez-Nieves, et al.  Dalton Trans.  2012, 41,12733).  Also for this type of systems, the thiol-eno addition of thiols that support ester or sulphonate groups makes it easier to reach dendritic molecules with anionic groups or their precursors (M.  Galán, E.  Fuentes-Paniagua, et al.  Organometallics, 2014,33,3977).  35 5DESCRIPTION OF THE INVENTION The present invention provides compounds formed by dendrons of carbosilane structure that are functionalized on their periphery with anionic groups (such as carboxylate, sulphonate or sulfate), which give the system a negative net charge, or cationic (such as ammonium). , which give the whole a positive net charge.  These dendrons have a focal point that contains a hydrophobic function, mainly a fatty acid derivative.  The fatty acid is bound to the dendron preferably through an ester bond, without ruling out other types of junctions, or even through electrostatic interactions.  The dendritic or dendron wedge refers to a very branched cone-shaped macromolecule that is defined by: 1.  a focal point; 20 2.  the units, branches or branches of growth, which start from said focal point; and 3.  the outer layer, surface or periphery of said branches that incorporates functional groups.  The skeleton and structure of these carbosilane dendrons with different focal points and peripheral anionic and cationic functions have been previously described (ES 2365685 82).  The term fatty acid refers to compounds known in this conventional manner: aliphatic acids found in natural fats and oils.  They are generally formed by chains containing 2 to 24 carbon atoms, preferably in the range of 6 to 18 carbon atoms.  The aliphatic chain can be linear or branched and has an acidic group such as carboxylic, sulphonate, phosphate, phosphonate 30 or the like, although it is preferably carboxylic.  Examples can be considered: capric, lauric, palmitic, stearic, oleic, linoleic and the like.  The fatty acids can be of natural or synthetic origin, they can have unsaturations or be saturated and optionally have positional or geometric isomers.  Many fatty acids are commercially available, or can be obtained from natural sources or by synthetic procedures known to those skilled in the art.  6The process for obtaining carbosilane dendrons with fatty acid derivatives at the focal point can be performed in different ways, some of which are described below.  5 A preferred embodiment comprises the reaction of the fatty acid with a dendron having a halogen, or other group that fulfills the same function, at the focal point in the presence of a base; or the same type of reaction but using a salt of fatty acid.  Another preferred embodiment comprises the reaction of the fatty acid with a dendron having a hydroxyl group or an amino group at the focal point in the presence of coupling agents.  These procedures can be performed in various solvents such as tetrahydrofuran, acetonitrile, dimethylformamide, dichloromethane or others, or mixtures thereof, heating or at room temperature.  With respect to the coupling agents for the formation of the ester bond, between an acidic group and an alcohol, or of the amide bond, between an acidic group and an amine, they are known to any person skilled in the art.  15 Synthesis processes can be performed from wedges with the final surface groups already present (anionic or cationic).  They can also be carried out in precursors or intermediates of the final compounds, so that after introducing the fatty acid or its derivative at the focal point of the dendron, the periphery of the latter is functionalized, following the procedures used to prepare the functionalized dendrons previously described, or similar ones that lead to the same final products (ES 2365685 82).  Therefore, a first aspect of the present invention relates to a dendron or dendritic wedge (from now on compound of the invention) comprising: A highly branched macro molecule that is defined by an outer layer, surface or periphery that incorporates functional groups, by a focal point and by the units, branches or branches of growth, internal structure, which start from said focal point and that serve as support for the dendritic periphery.  In addition, fatty acids are linked through the focal point.  35 a) The outer layer of the dendron consists, totally or partially, of equal or different units of the group of formula (1): 75 10 15 -Si-fR2) I P (R)) 3-p (1) where: a Rl is an alkyl group (Cl-C4).  preferably Rl is a methyl group; a p is an integer and varies between 1 and 3.  preferably p is 2; and R2 is the following group - (CH2kS- (CH2) and -R3; ax represents an integer that varies from 2 to 5; preferably x is 2 or 3; a and represents an integer that varies from 1 to 10; preferably and it varies between 1 and 5; a R3 is a -OH group.  -S03H.  -OS03H.  -COOR 'or -NR. .  R ·. . .  where R '.  R "and R. . . .  independently represent a (C1-C4) alkyl group or a hydrogen; or any of its salts.  a When R3 is -NR. .  R ·. . .  preferably R "and R ·. . .  independently represent an alkyl (Cl-C4) or hydrogen group.  more preferably an alkyl (Cl-C2) or hydrogen group.  even more preferably R3 is a group -N (CH3) 2 or a group -NH2.  Even more preferably x is 2 and even more preferably y is 2.  In a more preferred embodiment.  when R3 is -NR. .  R ·. . .  R2 is the group - (CH2) 2-S- (CH2) 2-N (CH3) 2 or - (CH2) 2-S- (CH2) 2-NH2.  The compound of the present invention can also be cationic.  forming ammonium groups (for example -NH3 + or -NMe /).  that is to say.  when R3 is an amino group.  or anionic.  forming the carboxylate groups.  sulfate or sulphonate.  for the rest of the R3 groups described above.  25 When R3 is a group -C02R ·.  or any of its salts.  preferably R 'is H or CH3.  more preferably x is 2 or 3.  and even more preferably and is 1 or 2.  30 When R3 is a group -S03H or -OS03H.  or any of its salts.  preferably x is 2 or 3.  and more preferably and is 2 or 3.  The term "alkyl" refers in the present invention to aliphatic chains.  linear or branched.  which have 1 to 4 carbon atoms.  for example.  methyl.  ethyl.  n-propyl.  i-8propyl, n-butyl, tert-butyl or sec-butyl, preferably has 1 to 2 carbon atoms, more preferably the alkyl group is a methyl.  Therefore, the present invention not only includes the compounds themselves, but any of their salts, for example, alkali metal or alkaline earth metal salts, for example they can be selected from sodium, potassium or calcium salts.  Preferably the salts are sodium or halogen salts, which can be selected from chloride, bromide, iodide salts; or triflate.  Preferably the salts are iodide and chloride.  10 b) The focal point can be selected from the group of formula (11): 15 20 25 30 - (CH2) z and -C (O) -R5 (11) where: oz is an integer that varies from 1 to 10, preferably z ranges from 1 to 5 and more preferably z is 3 or 4; or y is an atom or group of atoms that binds between the dendritic wedge and the fatty acid or its derivative, preferably Y = O, NH, S; or R5 is the fatty acid substituent chain (R5C02H) or its derivative, preferably R5 = - (CH2) aMe, a is an integer that ranges from O to 30.  o The chain (CH2) z is attached to a silicon atom corresponding to the periphery of the wedge (group (1)) or to the internal structure of the wedge (group (111)).  c) The internal structure of the dendron is constituted by units of the type: Sif-R6) I p (R1) 3-p (111) where: o the Si atom is attached to the focal point chain (group 11); y o R6 = - (CH2) b-, b represents an integer that varies from 1 to 10; preferably b is 2 or 3.  o The chain R6 = (CH2) b can be attached to another unit 111 or to the Si atom of the peripheral group (group 1).  95 The presence of type 111 units between the peripheral group (1) and the focus group (11) corresponds to dendritic generations.  So if there is no type unit (111) it would be generation 1, if there is a type unit (111) it would be generation 2 and so on.  Another aspect of the present invention relates to the process for obtaining the compounds of the invention.  In a preferred embodiment of the process of the invention, the synthesis comprises a reaction of a precursor dendron having a C-X bond at the focal point (X = halogen) with the fatty acid in the presence preferably of a base.  The periphery of the dendron may contain the definitive functional groups or their precursors.  In the latter case, the subsequent functionalization is performed as already described (W020111 01520; ES 2365685 B2).  As the reaction solvent, among others, acetone, dimethylformamide, tetrahydrofuran, acetonitrile or others that fulfill this function or mixtures of these solvents or with others can be used.  As a base, NaOH, KOH, K2C03 can be used; NElJ or others that fulfill this same function.  The synthesis of these dendrons can be represented, in general, by scheme 1, dendron already functionalized, or by scheme 2, dendron without functionalization.  In another preferred embodiment, the synthesis of these compounds can be carried out by coupling between the fatty acid and a dendron having a focal point with a group -OH, -NH2 or the like.  The periphery of the dendron may contain the definitive functional groups or their precursors.  In the latter case, subsequent functionalization is performed 25 as already described (W020111 01520; ES 2365685 B2).  As the reaction solvent, among others: acetone, dimethylformamide, tetrahydrofuran, acetonitrile, dichloromethane or others that fulfill this function or mixtures of these solvents or with others can be used.  As coupling agents, carbodiimides, or others that fulfill this function, can be used in the presence of a base such as dimethylaminopyridine or others.  The synthesis of these 30 dendrons can be represented, in a general way, by scheme 3, already functional dendron raised, or by scheme 4, undefunctional dendron.  x x S ~ R3) or XGnCx (F) or 105 XGnCx (F) or + R5C02H --' ---- _ or R5C02-GnCx (F) or R5C02GnCx (F) or Scheme 1.  Synthesis of carbosilane dendrons with pre-functionalized focal point fatty acid (X = CI, Br, 1, among others).  i) Base.  XGnVo i) Ó + R5C02H ---'-- XGnAo R5C02-GnVo OR R5C02-GnAo ii) Scheme 2.  Synthesis of carbosilane dendrons with fatty acid at the focal point and subsequent functionalization (X = CI, Br, 1, among others).  i) Base; ii) HS (CH2) and R3.  Where: 10 o Dendrons with fatty acids at the focal point are defined as 15 20 R5C02GnCx (F) or, where: o n indicates the number of generation G.  or Cx, indicates the length of the carbon chain between the atom of Si and S.  For example, when we start from the compound XGnVo (V = vinyl), Cx is C2, or when we start from XGnAo (A = allyl), Cx is C3 and so on.  o The compounds XGnVo and XGnAo of the following examples are described in: J.  Sánchez-Nieves, P.  Ortega, M.  TO.  Muñoz-Fernandez, R.  Gomez, F.  J.  of the Mata.  Tetrahedron 2010, 66, 9203; TO.  W.  van der Made, P. w.  N.  M van Leeuwen.  J.  Chem  Soc. Chem  Commun.  1992,1400; AND.  Fuentes-Paniagua, C.  AND.  Peña-González, M.  Galán, R.  Gomez, F.  J.  de la Mata, J.  Sánchez-Nieves.  Organometallics 2013, 1789.  or F, indicates the nature of the functional groups located on the periphery of the dendron (R3 = C02-, S03-, OS03-, S03H, OS03H, C02Me, C02H, OH, NH3 +, NMe2W, NMe3 +, NH2, NMe2) and " or "the number of these functional groups, which will depend on the number of generations.  or R5C02 indicates the type of fatty acid used for the synthesis.  On the other hand, obtaining cationic compounds with terminal ammonium groups, for example NMe3 +, can be produced by a quaternization reaction of the corresponding amino group using an RX derivative, dialkyl sulfates (Cl-C5), methyl triflate, or any of its combinations as a quaternizing agent (where R is selected from hydrogen, alkyl (Cl-C24), alcohol (Cl-C24) or an aryl, 11preferably benzyl; and X is a halogen, preferably CI, Br or 1), such as, for example, methyl iodide (Mel), HCI, methyl chloride, methyl bromide, ethyl chloride, ethyl bromide, propyl chloride, hexyl chloride, dodecyl chloride, benzyl chloride, benzyl bromide, ethanol bromide, ethanol iodide (HO-CH2CH2-I) or any of its combinations.  Also, in the case of functional compounds hoisted with ammonium groups of the NR2 · HCI type, they are neutralized with basic medium and subsequently can be quaternized with other alkylating agents such as those described above.  In another preferred embodiment, the synthesis of these compounds can be carried out by coupling between the fatty acid and a dendron that has a focal point with a group -OH, -NH2 or similar and at the periphery of the dendron the definitive functional groups.  As reaction conditions, those described in this invention can be used for similar compounds, without discarding other solvents or coupling agents.  The synthesis of these dendrons can be represented, in general, by scheme 3.  15 20 R5C02GnCx (F) or Scheme 3.  Synthesis of carbosilane dendrons with pre-functionalized fatty acid at the focal point (X = OH, NH2, among others).  i) Base, carbodiimide.  i) R5C02-GnVo ii) - ~ - ~.  Ó - ~ --XGnVo Ó + R5C02H XGnAo R5C02-GnAo Scheme 4.  Synthesis of carbosilane dendrons with fatty acid at the focal point and subsequent functionalization (X = OH, NH2, among others).  i) Base, carbodiimide; ii) HS (CH2) and R3.  Where dendrons with fatty acids at the focal point R5C02GnCx (F) or defined as set forth above for schemes 1 and 2.  The present invention also includes the preparation of Janus type dendrimers.  These dendrimers are characterized by being formed by two dendritic units that have some distinct structural characteristic.  In this case, Janus type 30 dendrimers are formed by two types of carbosilane dendrons, one functionalized with cationic or anionic groups, such as those described above in this invention, and another functionalized at the periphery with fatty acids or derivatives thereof.  12 generationsr5 of each dendron may be the same or different.  The outer layer of this second dendron consists, totally or partially, of equal or different units of the group of formula (IV): -Yes - (- R7) IP (Rl) 3-p (IV) where: or R1 is a (C1-C4) alkyl group, preferably R1 is a methyl group; or p is an integer and varies between 1 and 3, preferably p is 2; y or R7 is the following group - (CH2) x-S- (CH2) and -Y-C (O) R5; 10 or x represents an integer that varies from 2 to 5; preferably x is 2 or 3; or y represents an integer that varies from 1 to 10; preferably and varies between 1 and 5; or YC (O) R5 represents a fatty acid or its derivative, as defined above for R5 and Y.  15 o The union between the two units of the Janus type dendrimer can be selected from the group - {CH2) c-R8_ (CH2) C ', where: ocyc' is an integer that varies from 1 to 10, preferably varies from 1 at 5 and more preferably they are 3 or 4; also c and c 'may or may not be equal to each other; or R8 is any type of joint, preferably of the type -OR90-; where R9 is any hydrocarbon group, preferably R9 is an aromatic group of the type Janus type dendrimers of the invention can be prepared by coupling each of the wedges to the R8 group.  The order of engagement of the wedges 25 is indistinct.  The reaction can be carried out in solvents such as acetone, DMF, THF or others or mixtures thereof, in the presence of a base, such as K2C03, Na2CO, CSC03, NaHC03 without discarding others, preferably by heating.  Also the preparation of Janus dendrimers can be carried out by introducing a wedge with the fatty acid functions in the periphery and another with olefin groups.  Again the order of introduction of 30 wedges is indistinct.  From the Janus dendrimer containing olefin functions, obtaining the compounds of the invention occurs through a thiol-eno reaction with a thiol derivative containing the anionic or cationic group, or a precursor thereof, as described. in the previous sections of this invention (scheme 5).  The 13The solvents and conditions used for the preparation of any of these systems are known to any person skilled in the art and similar to the conditions described for the dendrons of the invention.  S ~ OH I ~ S 'Br ~' '------ S ~ OH + 1.  ASD / O '/ 1h I ~ S or ~ o) l. . (CHv ,. Me 2.  rt.  24h Br ~ Si '----- S "' v0 - y (CH2) ,. I Acetone 90'C 24h or BrG, C3 (C02 (CH2) ,. CH3h Scheme 5.  Example of preparation of a Janus type dendrimer with first generation anionic dendrons and palmitic acid.  Another aspect of the invention reflects the ability of the described compounds to form 10 micelles.  These micelles can be formed from the dendrons of the invention in suitable concentrations, by combination of dendrons of carbosilane nature (W02011101520; ES 2365685 82) with fatty acids or from the Janus type dendrimers of the invention.  The main means for the formation of these systems would be aqueous, but other solvents and mixtures thereof can be used.  The micelles can also be formed in solutions containing soluble salts in these media or surfactants.  In a preferred embodiment, the formation of micelles is carried out by dissolving in water the compounds of the invention in concentrations from a so-called critical micellar concentration (eMe), which indicates precisely the aggregation of the 20 compounds to give rise to micelles.  This process can be determined by different techniques, such as conductivity measurements, without ruling out others.  The eMe of 14These systems may vary depending on the dendritic generation, focal point length, the type of peripheral group of the dendron, among other factors.  In another preferred embodiment, the formation of micelles is carried out by dissolving in an aqueous solution of salts, preferably NaCl but not ruling out others.  These types of solutions have greater ionic strength and favor micellar aggregation, that is, the value of the CMC decreases with increasing concentration of added salt (with increasing ionic strength).  This process can be determined by different techniques, such as surface tension measurements, without ruling out others.  The CMC of these systems may vary depending on the dendritic generation, focal point length and the type of dendron peripheral group, among other factors.  The present invention also relates to the uses in biomedicine of the compounds of the invention and the micelles formed by them.  Among them, the use of the 15 cationic derivatives as non-viral transport agents for the transfection or internalization of nucleic material inside different cell lines in gene therapy processes, the use of these cationic or anionic compounds as therapeutic agents "per" se ", for example as antibacterial, antiviral or antiprionic agents, or also their use as drug transporters.  In another preferred embodiment the systems of the invention, dendrimers, dendrons and micelles, mainly cationic ones, are used as antimicrobial agents.  Therefore, they can be used for the prevention and / or treatment of bacterial infections.  Also the systems of the invention, dendrimers, dendrons and micelles, mainly anionic ones, exhibit antiviral activity.  Because of this, they can be used for the prevention and / or treatment of diseases of viral origin, such as AIDS, Herpes, Influenza or others.  Taking into account the biocidal activity of the systems of the invention, dendrimers, dendrons and micelles, another aspect of the present invention relates to the use of them as biocidal agents for non-therapeutic applications, such as, but not limited to, prevent the appearance of microorganisms on surfaces or water treatment.  Another aspect of the present invention relates to the use of the systems of the invention,dendrimers, dendrons and micelles, both cationic and anionic, for the preparation of a medicament.  More preferably, the medicament is used for the prevention and / or treatment of diseases caused by microorganisms, such as viruses, bacteria, protozoa or fungi.  More preferably the prevention and / or treatment are 5 for diseases caused by HIV or bacterial infections.  Another aspect of the present invention relates to a pharmaceutical composition comprising at least one dendrimer, dendron or micelle as described above and a pharmaceutically acceptable carrier.  In addition, this pharmaceutical composition 10 may comprise another active ingredient, preferably an antibiotic, antiviral or anti-inflammatory.  The antibiotic can be from the group of beta-lactams, such as penicillin, or other non-beta-lactams such as erythromycin.  The anti-inflammatory can be for example ibuprofen and the antiviral AZT, but without ruling out others that fulfill similar functions.  The "pharmaceutically acceptable vehicles" that can be used in said compositions are the vehicles known to a person skilled in the art.  Examples of pharmaceutical preparations include any solid composition (tablets, pills, capsules, granules, etc.). ) or liquid (gels, solutions, suspensions or emulsions) 20 for oral, nasal, topical or parenteral administration.  For anionic dendrons or micelles, the administration will preferably be topical and even more preferably in the form of a gel.  In the case of cationic dendrons or micelles, preferably the administration will be oral, parenteral (injectable), or topical.  In another aspect, the present invention relates to a method of treatment or prevention of diseases caused by microorganisms, such as viruses, bacteria, protozoa or fungi in a mammal, preferably a human, comprising the administration of a therapeutically effective amount. of a composition comprising at least one dendritic compound or micelle of the invention.  Preferably, administration of the composition can be performed orally, nasally, topically or parenterally.  For anionic systems, preferably the administration will be topical and even more preferably in the form of a gel.  In the case of cationics, preferably the administration will be oral, parenteral (injectable) or topical.  16In the sense used in this description, the term "therapeutically effective amount" refers to the amount of the composition calculated to produce the desired effect and, in general, will be determined, among other causes, by the characteristics of the composition itself, the age, condition and history of the patient, the severity of the disease, 5 and the route and frequency of administration.  Another aspect of the present invention relates to the use of the cationic dendrons or micelles of the invention as a non-viral vector.  Preferably, the vector is used for transfection or internalization of nucleic material in gene therapy processes, that is, the compounds of the invention can act as transfection agents in gene therapy.  By "nucleic material" refers in the present invention to a material, isolated and / or purified, comprising a nucleotide sequence and can be selected from 15 oligonucleotides, siRNA or AON.  Another aspect of the present invention relates to the use of the non-viral vector of the invention, for the preparation of a medicament.  More preferably, for the preparation of a medicament for the treatment by gene therapy of HIV infection or cancer.  It is also possible to use the systems of the invention, dendrons and micelles, as vehicles for transporting molecules, preferably molecules with pharmacological activity (active ingredients), and more preferably anionic or cationic molecules, depending on whether the compound is cationic or anionic respectively .  The active substance 25 can be an antibiotic, an anti-inflammatory or an antiviral, including for example and not limited to an antibiotic from the beta-lactam group, such as penicillin, to an anti-inflammatory such as ibuprofen or an antiviral such as AZT.  The characteristics of the micelles mean that they can also act as transporters for drugs that are not soluble in aqueous media.  Throughout the description and the claims the word "comprises" and its variants are not intended to exclude other technical characteristics, additives, components or steps.  For those skilled in the art, other objects, advantages and characteristics of the invention will be derived partly from the description and partly from the practice of the invention.  The 17The following examples and figures are provided by way of illustration, and are not intended to be limiting of the present invention.  DESCRIPTION OF THE FIGURES Figure 1.  Dendron and 1 H-NMR spectrum (CDCb) of R5C02G1A2 (R5 = Me (CH2) 4).  Figure 2  First to third generation cationic dendrons with palmitic acid at the focal point R5C02GnC2 (NMe3 +) m (R5 = Me (CH2) 14; n = 1, m = 2; n = 2, m = 4, n = 3, m = 8).  Figure 3  First to third generation cationic dendrons with hexanoic acid at the focal point R5C02GnC2 (NMe3 +) m (R5 = Me (CH2) 4; n = 1, m = 2; n = 2, m = 4, n = 3, m = 8).  Figure 5  First to third generation anionic dendrons with carboxylate functions on the periphery and with palmitic acid at the focal point R5C02GnC3 (C02-) m (R5 = Me (CH2) 14; n = 1 m = 2 · n = 2 m = 4 n = 3 m = 8) t I t II • Figure 6.  First to third generation anionic dendrons with sulfonate functions at the periphery and with palmitic acid at the focal point R5C02GnC3 (S03-) m (R5 = Me (CH2) 14; n = 1 m = 2 · n = 2 m = 4 n = 3 m = 8), t III • Figure 8.  Critical micellar concentration (CMC) determination of anionic dendrons R5C02GnC3 (S03-) m (R5 = Me (CH2) 14; n = 1, m = 2; n = 2, m = 4, n = 3, m = 8) by conductivity.  Figure 9  Critical micellar concentration (CMC) determination of cationic dendrons R5C02GnC2 (NMe3 +) 2 (R5 = Me (CH2) 14; n = 1, m = 2; n = 2, m = 4, n = 3, m = 8) by conductivity.  35 Figure 10.  Critical micellar concentration (CMC) determination of anionic dendrons 18R5C02GnC3 (S03-) m (R5 = Me (CH2) 4; n = 1, m = 2; n = 2, m = 4, n = 3, m = 8) by surface tension.  Figure 11  Study of the variation of the maximum absorbance of procaine hydrochloride 5 by varying the concentration of dendron in aqueous solution.  Figure 12  Toxicity of polyanionic dendrons by MTT assay in the TZM cell line. bl.  A 48 h post-treatment MTT test was performed with the different concentrations of the anionic systems.  An 80% cell viability limit was determined as a toxicity limit.  The data shown represent the average of five experiments performed in triplicate each.  Abbreviations: NT = Control not treated, DMSO = Dimethyl sulfoxide.  Figure 13  Inhibition of viral infection by polyanionic dendrons tested.  The cells were treated, in each case, with the maximum non-toxic concentrations mentioned in the previous figure.  The percentage of infection for each virus was determined 48 post-infection quantifying luciferase activity.  The data represent the mean ± standard deviation of three independent experiments performed in triplicate.  **: p <0.001, ***: p <0.0001 vs. infection control 20 Figure 14. Dose-response curves obtained for dendrons BDCG048 and BDCG054. Inhibition curve in (A) viral isolate R5 HIV-1NLAD8, and (B) viral isolate X4 HIV-1NL4.3. The cells were pre-treated with increasing concentrations of 0.01 to 1 O.M of dendron for 1 hour. They were subsequently infected with 20 ng HIV-1/106, for both viral isolates, for 3 hours. The percentage of infection was quantified after 48 hours. The data 25 represent the average of three experiments performed in triplicate each. Figure 15. Effect of the addition of the BDCG048 and BDCG054 dendrons in the HIV-1 viral cycle. TZM.bl cells were infected with 20 ng R5 HIV-1NLADa / 106 TZM.bl. Subsequently, the cells were treated with dendrons at different times after infection. Finally, the infection was quantified at 48 hours following the previously described procedure. T-20 (enfurvitide, 20¡.¡M), TFV (tenofovir, 1¡.¡M), RAL (raltegravir, 1¡.M), BDCG048 (1 O¡.¡M) and BDCG054 (1 were used O¡.M). Data are represented as the average of three experiments. 19EXAMPLES The structures of some dendrons and their NMR spectra are found in Figures 1-7. The following describes the synthesis of some of the compounds of the invention (scheme 6) that are representative of the rest of the systems included in the invention. o Br ~) m [~ o ~) m [~ OH + w W W = 15 n- 'f1l' "2 <'} W & 5n-' m-2 (4) Wo-15 nz2 rn-4 (2) Wa5 n-2 mz.4 (5) ..... '50 -3_ (3) W-Sn-3 ~ (8) 1 iI or (i) [~ O s ~ NMe2HCI) mw Wa15 n- 'm-2 W> IN - = $ n "' 1 m-2 (10) W-15n-2", ... } "" 5ns2rn-.4 ~ '1) W'-15 0-3 rl'P'-8 (9) Wz5 n "' 3 m-8 12): 1 OO (i) [~ OS ~ NMe2) Iv [~ O s ~ NMe31) wmw 'W-15n-' m-2 ~ '3 ~ V'JIo: S n: 1 fTP2 (t6) W-15 n-1 nP2 (19) VP5n-, m = 2 ~ ! Na15n = 2m: a.4 14 ws n-2 mz4 (17) VoJa15 n-2 rn = 4 (20) VP5 n-2 rn = 4 (23 W = 15 n = 3 ~ 8 (15) w-5 n-31ll ' <8 (18) ll. k15 n-3 m = 8 (21) 'i'P5 n-3 ",", 8 (24) 10 Scheme 6.  Synthesis of cationic dendrons.  (i) Acetone, K2C03, Crown Ether 18-C-6, 24h; (ii) THF / MeOH, HS (CH2) 2NMe2HCI, DMPA, hv, 4h; (iii) NaOH; (iv) Mel 24h.  Example 1. -Functional dendrons hoisted with vinyl groups.  15 Synthesis of RC02G1 ~ (R = Me (CH2) 14) (Figure 1).  Method A) Mix in a BrG1A2 vial (1. 0 g, 4. 29 mmol), K2C03 (1. 18 g, 8. 58 mmol), crown ether 18-C-6 (0. 11 g, 0. 42 mmol) palmitic acid (1. 10 g, 4. 29 mmol) and dissolve in acetone (50 ml) at 90 ° C, under Argon atmosphere with continuous stirring for 24 hours.  After this time the acetone is evaporated from the reaction crude and the products are extracted using a mixture of EhO and H20 saturated with NaCl.  The organic phase is dried over MgSO4 for 15 minutes and then in the presence of Si02 for another 10 minutes.  The solution is filtered using celite and the reaction residues are evaporated in vacuo to obtain the dendrons modified with fatty acids at the focal point as 25 orange oils with high yields (1. 5 g, 86%).  20 mNMR (CDCh): 1H NMR 6 0. 09 (s, 3H, SiMe), 0. 60 (t, 2H, OCH2CH2CH2CH2Si), 0. 81 (t, 3H, CH3 {CH2) 14C02), 1. 21 (s, 24H, CH3 (CH2) I ~ CH2) 2C02), 1. 36 (m, 2H, OCH2CH2CH2CH2Si), 1. 58 (m, 4H, OCH2CH2CH2CH2Si, CH3 (CH2) 12CH2CH2C02), 2. 22 (t, 2H, CH3 (CH2) 12CH2CH2C02), 4. 00 (t, 2H, OCH2CH2CH2CH2Si), 5. 66 (m, 2H, SiCHCH2), 5. 97 5 (m, 4H, SiCHCH2).  NMR-13C (CDCh) 6 -5. 5 (SiMe), 13. 4 (OCH2CH2CH2CHzSi), 14. 0 (CH3CH2CH2 (CH2) 1OCH2CH2C02), 20. 0 (OCH2CH2CH2CH2Si), 22. 6 (CH3CH2CH2 (CH2) 1OCH2CH2C02), 24. 9 (CH3CH2CH2 (CH2) 1OCH2CH2C02), 29. 0-29. 6 (CH3CH2CH2 (CH2) IOCH2CH2C02), 31. 8 (CH3CH2CH2 (CH2) 10CH2CH2C02), 32. 2 (OCH2CH2CH2CH2Si), 34. 2 (CH3CH2CH2 (CH2) 1OCH2CH2C02), 63. 7 (OCH2CH2CH2CH2Si), 10 132. 8 (SiCHCH2), 136. 5 (SiCHCH2), 173. 7 (CH3CH2CH2 (CH2) 1OCH2CH2C02).  MS: [M + Hj + = 409. 35 uma  Anal.  Calculated for C2sH4802Si (408. 78 g / mol)%: C, 73. 46, H, 11. 84.  Exp.  %: C, 72. 95, H, 11. 37.  Method B) A dendron of type HO (CH2) zOG1A2 (1. 00 g, 4. 12 mmol) is reacted with palmitic acid (0. 95 g, 3. 71 mmol) in CH2CI2 (50 ml) in the presence of a carbodiimide (DCC, 4. 12 mmol) and a base (DIPEA, 4. 12 mmol) for 24 hours at room temperature.  After this time the volatiles are evaporated and the compound RC02 (CH2hOG1 ~ is purified by means of a silica column (0. 98 g, 65%).  20 Example 2. -Dendrons functionalized with cationic groups or their precursors.  Method A) The dendron with vinyl groups on the periphery RC02G1CN2 (R = Me (CH2) 14) (1. 0 25 g, 2. 44 mmol), is coupled with 2- (dimethylamino) ethanethiol hydrochloride (0. 76 g, 5. 38 mmol) and 5 mol% DMPA (0. 07 g, 0. 26 mmol), in a solution of THF / MeOH (75:25) (5 ml).  The reaction mixture is deoxygenated and irradiated for 2 hours under ultraviolet light.  After this time another portion of DMPA corresponding to 5 mol% is added, and the reaction mixture is irradiated again for two more hours with UV light.  The progress and completion of it were monitored by 1 H NMR.  The solvents are evaporated and the reaction product is dissolved in distilled water and purified by ultrafiltration with cellulose membranes with a pore size between 500-1000 Da.  The compound obtained is neutralized with a solution of 1 M NaOH and extracted with diethyl ether (3 x 20 mL).  The organic phase is dried using anhydrous magnesium sulfate for 1 h, filtered and 21removed under vacuum to obtain the desired compound as a yellow oil with good yields (1. 34 g, 99%).  NMR (COCb): 1H NMR 6-0. 09 (s, 3H, SiMe), 0. 43 (t, 2H, OCH2CH2CH2CH2Si), 0. 84 (m, 5 7H, CHJ {CH2) 14C02, SiCH2CH2S), 1. 25 (s, 24H, CH3 (CH2) 12 (CH2hC02), 1. 30 (m, 2H, OCH2CH2CH2CH2Si), 1. 58 (m, 4H, OCH2CH2CH2CH2Si, CH3 (CH2) 12CH2CH2C02), 2. 24 (s, 14H, SCH2CH2NMe2, CH3 (CH2) 12CH2CH2C02), 2. 48 (m, 4H, SCH2CH2NMe2), 2. 57 (m, 4H, SCH2CH2NMe2), 2. 62 (m, 4H, SiCH2CH2S), 4. 00 (t, 2H, OCH2CH2CH2CH2Si).  NMR-13C (COCb) 6 -5. 6 (SiMe), 12. 9 (OCH2CH2CH2CH2Si), 13. 9 (SiCH2CH2S), 14. 2 10 (CH3CH2CH2 (CH2) 1OCH2CH2C02), 20. 0 (OCH2CH2CH2CH2Si), 22. 4 (CH3CH2), 23. 3 (SCH2CH2NMe2), 24. 7 (CH3CH2), 29. 4-28. 9 (CH3CH2CH2 (CH2) 1OCH2CH2C02), 29. 4 (SiCH2CH ~), 31. 6 (CH3CH2CH2 (CH2) 1OCH2CH2C02), 33. 0 (OCH2CH2CH2CH2Si), 34. 2 (CH3CH2CH2 (CH2) 10CH2CH2C02), 45. 0 (SCH2CH2NMe2), 58. 9 (SCH2CH2NMe2), 63. 7 (OCH2CH2CH2CH2Si), 173. 7 (CH3CH2CH2 (CH2) 1OCH2CH2C02).  Anal.  Cale.  for 15 C33H7oN202S2Si (619. 14 g / mol)%: C, 64. 02, H, 11. 40, S, 10. 36.  Exp.  %: C, 62. 15, H, 10. 70, S, 8. 90.  Method B) A dendron of type HO (CH2) 20G1 C2 (NMe2h (0. 50 g, 1. 11 mmol) is reacted with palmitic acid (0. 33 g, 1. 13 mmol) in CH2Cb (25 ml) in the presence of a carbodiimide (OCC, 1. 13 mmol) and base (OIPEA, 1. 13 mmol) for 24 hours at room temperature.  After this time the volatiles are evaporated and the compound RC02 (CH2hOG1C2 (NMe2h is purified by silica column (44%)).  To a solution of the neutral compound RC02G1C2 (NMe2h (R = Me (CH2) 14) (1. 34 g, 2. 16 mmol) Mel was added in excess (0. 54 mi, 8. 64 mmol).  The resulting solution was maintained for 12 h with constant stirring at room temperature and then evaporated under reduced pressure thus obtaining the quaternized compound as a white solid with high yield (1. 84.95%).  NMR (020): 1 H NMR 60. 04 (s, 3H, SiMe), 0. 60 (m, 2H, OCH2CH2CH2CH2Si), 0. 84 (m, 7H, CH3 (CH2) 14C02, SiCH2CH2S), 1. 22 (s, 24H, CH3 (CH2) 12 (CH2) 2C02), 1. 30 (m, 2H, OCH2CH2CH2CH2Si), 1. 67 (m, 4H, OCH2CH2CH2CH2Si, CH3 (CH2) 12CH2CH2C02), 2. 24 (m, 2H, CH3 (CH2) 12CH2CH2C02), 2. 62 (m, 4H, SiCH2CH2S), 2. 86 (m, 4H, SCH2CH2NMe3 +), 3. 12 (m, 18, NMe3 +), 3.58 (m, 35 4H, CH2CH2NMe3 +), 3. 85 (m, 2H, OCH2CH2CH2CH2Si).  NMR-13C (020) 6 -5. 7 (SiMe), 2212. 9 (OCH2CH2CH2CH2Si), 13. 9 (SiCH2CH2S), 14. 2 (CH3CH2CH2 (CH2) 1OCH2CH2C02), 20. 0 (OCH2CH2CH2CH2Si), 22. 4 (CH3CH2CH2 (CH2) 1OCH2CH2C02), 23. 3 (SCH2CH2NMe3 +), 24. 7 (CH3CH2CH2 (CH2) 1OCH2CH2C02), 29. 4-28. 9 (CH3CH2CH2 (CH2) 1OCH2CH2C02), 29. 4 (SiCH2CH2S), 31. 6 (CH3CH2CH2 (CH2) 1OCH2CH2C02), 33. 0 (OCH2CH2CH2CH2Si), 34. 2 5 (CH3CH2CH2 (CH2) 1OCH2CH2C02), 53. 6 (SCH2CH2NMe3 +), 63. 7 (OCH2CH2CH2CH2Si), 65. 1 (SCH2CH2NMe3 +), 173. 7 (CH3CH2CH2 (CH2) 1OCH2CH2C02).  Anal.  Calc.  for C3sH76hN202S2Si (903. 03 g / mol)%: C, 46. 55, H, 8. 48, S, 7. 10.  Exp.  %: C, 46. 03, H, 8. 29, S, 5. 90.  10 Example 3. -Dendrons functionalized with anionic groups or their precursors.  15 W = 15. = 1 m = 2 (1) W = 15. = 2 m = 4 (2) W = 15. = 3 m = 8 (3) W = 15. = 1 m = 2 (4) W = 15. = 2 m = 4 (5) W = 15. = 3 m = 8 (6) W = 5. = 1 m = 2 (7) W = 5. = 2 m = 4 (8) W = 5. = 3 m = 8 (9) W = 5. = 1 m = 2 (10) W = 5. = 2 m = 4 (11) W = 5. = 3 m = 8 (12) Scheme 7.  Synthesis of anionic dendrons.  (i) Acetone, K2C03, Crown ether 18-C-6, 24h; (ii) THF / MeOH, HS (CH2hS03Na, DMPA, hv, 4h.  Method A) BrG1A2 (0. In a blister under an inert atmosphere) 50 g, 1. 91 mmol), K2C03 (0. 52 g, 3. 83 mmol), crown ether 18-C-6 (0. 05 g, 0. 19 mmol) and palmitic acid (0. 49, 20 0. 19 mmol) and dissolve in acetone (50 ml) at 90 ° C, under Argon atmosphere with continuous stirring for 24 hours.  After this time the acetone is evaporated and the products are extracted using an Et20 and H20 mixture saturated with NaCl.  The organic phase is dried over MgSO4 and then in the presence of Si02 for a further 10 minutes.  The solution is filtered using celite and the reaction residues evaporated in vacuo.  The compound obtained (0. 50 g, 1. 14 mmol) is dissolved in a THF / MeOH mixture (75:25) and combined with a solution of sodium 3-mercapto-1-propanesulfonate (0. 45 g, 2. 51 mmol) in 5 ml of previously prepared water.  On this final mixture, the DMPA photoinitiator (0. 06 g, 0. 25 mmol).  The mixture is 23deoxygenates each time this process is performed and is irradiated with UV light (365 nm).  The total reaction time is 4 hours.  The solvents are evaporated and the reaction product is dissolved in distilled water and purified by ultrafiltration with cellulose membranes of pore size between 500-1000 Da.  Finally the water is removed and the product is obtained as a white solid with high yield (0. 82 g, 91).  NMR (020): 1H NMR ~ -0. 13 (m, 3H, SiMe), 0. 53 (m, 6H, OCH2CH2CH2CH2Si, SiCH2CH2CH2S), 0. 75 (m, 3H, CH3 (CH2) 14C02), 1. 15 (m, 26H, CH3 (CH2) 12 (CH2) 2C02, OCH2CH2CH2CH2Si), 1. 47 (m, 8H, CH3 (CH2) 12CH2CH2C02, OCH2CH2CH2CH2Si, 10 SiCH2CH2CH2S), 1. 89 (m, 4H, SCH2CH2CH2S03,), 2. 14 (m, 2H, CH3 (CH2) 12CH2CH2C02), 2. 44 (m, 4H, SiCH2CH2CH2S), 2. 52 (m, 4H, SCH2CH2CH2S03), 2. 85 (m, 4H, SCH2CH2CH2S03), 3. 92 (m, 2H, OCH2CH2CH2CH2Si).  NMR-13C (020) ~ -5. 35 (SiMe), 12. 8 (SiCH2CH2CH2S), 13. 2 (OCH2CH2CH2CH2Si), 13. 92 (CH3 (CH2) 12CH2CH2C02), 20. 1 (OCH2CH2CH2CH2Si), 23. 9 (SiCH2CH2CH2S), 24. 5 (SCH2CH2CH2S03), 24. 9 15 (CH3 (CH2) 1OCH2CH2C02), 29. 3-29-9 (CH3 (CH2) 12CH2CH2C02), 30. 29 (SCH2CH2CH2S03), 32. 3 (OCH2CH2CH2CH2Si), 34. 1 (CH3 (CH2) 12CH2CH2C02), 35. 2 (SiCH2CH2CH2S), 50. 1 (SCH2CH2CH2S03), 63. 9 (OCH2CH2CH2CH2Si), 173. 3 (CH3CH2CH2 (CH2) 10CH2CH2C02).  Anal.  Cale.  For C33H66Na20sS4Si (793. 20 g / mol)%: C, 49. 97, H, 8. 39, S, 3. 54  Exp.  %: C, 49. 15, H, 7. 95, S, 2. 35  20 Method B) A dendron of type HO (CH2) 20G1 C3 (S03Na) 2 (0. 250 g, 0. 44 mmol) is reacted with palmitic acid (0. 256 g, 0. 88 mmol) in OMF (15 ml) in the presence of a carbodiimide (EOCI, 0. 88 mmol) and base (OMAP, 0. 88 mmol) for 24 hours at 60 ° C.  After this time the volatiles are evaporated and the compound RC02 (CH2hOG1C3 (S03Na) 2 is purified by dialysis (21%).  500 mg of RC02G1A2 (1.14 mmol) are dissolved in 2 mL of THF.  On this solution, 0.20 mL of 3-mercaptopropionic acid (2.28 mmol) and 58.4 mg of OMPA (0.228 mmol) are added.  Finally, the solution is kept under stirring for 4 hours under ultraviolet light.  1H NMR (C0300): 0.04 (s, 3H, (CH2hSi (CH3)), 0.70 (m, 6H, (CH2hSi (CH3)), 0.94 (t, 3H, CH3 (CH2) 14C02 ), 1.34 (s, 26H, CH3 (CH2) 12 (CH2) 2C02 + C02 (CH2) 2CH2), 1.65 (m, 8H, SiCH2CH2CH2S + C02CH2CH2 + CH2CH2C02), 2.35 (t, 2H, CH2CH2C02), 2.61 (m, 245 8H, SiCH2CH2CH2S + SCH2CH2C02H), 2.78 (t, 4H, SCH2CH2C02H), 4.12 (t, 2H, C02CH2 (CH2) JSi).  500 mg of RC02G1C2 (C02Hh (0.77 mmol) are dissolved in 2 mL of THF.  To this solution another solution of 129.4 mg of NaHC03 (1.54 mmol) in water is added.  Finally, the solution is kept under stirring for 30 minutes.  1H-NMR (020): 0.08 (s, 3H, (CH2) 3Si (CH3 », 0.55 (m, 6H, (CH2) 3Si (CH3», 0.82 (t, 3H, CHJ (CH2) ) 14C02), 1.13 10 (s, 26H, CH3 (CH2) 12 (CH2) 2C02 + C02 (CH2) 2CH2), 1.46 (m, 8H, SiCH2CH2CH2S + C02CH2CH2 + CH2CH2C02), 2.17 (t , 2H, CH2CH2C02), 2.42 (t, 4H, SiCH2CH2CH2S), 2.49 (t, 4H, SCH2CH2C02Na), 2.64 (t, 4H, SCH2CH2C02Na), 3.94 (t, 2H, C02CH2 (CH2 ) 3 Yes).  Example 4 - Janus type dendrimers functionalized with dendrons sulfonate v 15 palmitic acid.  BrG1C3 (OH) 2.  BrG1A2 (1. 0 g, 3. 83 mmol) using a THF / MeOH mixture (75:25, 20 ml) together with a solution of 2-mercaptoethanol (0. 08 g, 0. 95 mmol) at 0. 5 ml of THF prepared previously.  The photoinitiator 2,2 dimethoxy-2-phenylacetophenone, OMPA (0. 05 g, 0. 19 mmol), is added on the dendron solution.  The mixture is deoxygenated and irradiated with UV light (365 nm) for 1 hour.  After this time, photoinitiator and thiol are added again in the same initial amounts.  This process is repeated every hour until a total reaction time of 4 hours is completed.  The solvents are evaporated and the product obtained is purified by washing with water and hexane (3 x 15) to obtain BrG1C3 (OHh as a yellow oil (1. 4 g, 88%).  NMR (COCb): 1H-NMR 6-0. 07 (s, 3H, SiMe), 0. 45 (t, 2H, BrCH2CH2CH2CH2Si), 0. 56 (t, 3H, SiCH2 (CH2hS), 1. 37 (m, 2H, BrCH2CH2CH2CH2Si), 1. 51 (m, 4H, SiCH2CH2CH2S), 1. 80 (m, 4H, BrCH2CH2CH2CH2Si), 2. 47 (t, 4H, SiCH2CH2CH2S), 2. 65 (t, 4H, SCH2CH20H), 3. 36 (t, 2H, BrCH2CH2CH2CH2Si), 3. 65 (t, 4H, SCH2CH20H).  30 NMR-13C (COCb) 6 -5. 58 (SiMe), 12. 5 (BrCH2CH2CH2CH2Si), 13. 10 (SiCH2 (CH2hS), 22. 14 (BrCH2CH2CH2CH2Si), 24. 27 (SiCH2CH2CH2S), 33. 51 (BrCH2CH2CH2CH2Si), 34. 96 (SCH2CH20H), 35. 30 (SiCH2CH2CH2S), 36. 04 (BrCH2CH2CH2CH2Si), 60. 33 (SCH2CH20H).  MS: [M + Hr = 218. 22  Anal.  Calculated for C1sH33Br02S2Si (417. 54 g / mol)%: C, 43. 15, H, 7. 97.  Exp.  %: C, 45. 20, H, 7. 35  35 25I ~ S ~ OH S · Br ~ I ~ S ~ OH BrG1C3 (C02 (CH2) 14CH3) 2.  In a schlenk, the compound BrG1C3 (OHh (0. 10 g, 0. 23 mmol) and triethylamine (0. 08 g, 0. 72 mmol) are dissolved in CH2CI2 (50 ml) and the O ° C solution is stirred under an inert atmosphere for 1 hour.  After this time, 5 Palmitoyl Chloride (0. 14 g, 0. 52 mmol) on this solution keeping the reaction with constant stirring at room temperature for 24 hours.  The solvent is evaporated in vacuo and the product is extracted using Et20 and a solution of water saturated with NaCl.  The organic phase is dried over MgSO4 and filtered through Celite.  The product obtained is purified using a size exclusion chromatography column (Bio-Beds S-X1) using 10 THF as eluent, thus obtaining BrG1C3 (C02 (CH2) 14CH3h as a yellow oil (0. 19 g, 89%).  NMR (CDCb): 1HRMN ~ -0. 07 (m, 3H, SiMe), 0. 49 (t, 2H, BrCH2CH2CH2CH2Si) 0. 56 (m, 4H, SiCH2 (CH2) 2S), 0. 82 (m, 6H, CHJ (CH2) 14C02), 1. 19 (s, 50H, CH3 (CH2) 12 (CH2) 2C02, BrCH2CH2CH2CH2Si), 1. 47 (m, 6H, CH3 (CH2) 12CH2CH2C02, SiCH2CH2CH2S), 1. 80 (t, 2H, BrCH2CH2CH2CH2Si), 2. 25 (m, 4H, CH3 (CH2) 12CH2CH2C02), 15 2. 51 (m, 4H, SiCH2CH2CH2S), 2. 67 (m, 4H, SCH2CH2C02), 3. 36 (m, 2H, BrCH2CH2CH2CH2Si), 4. 15 (t, 4H, SCH2CH2C02).  NMR-13C (CDCb) ~ -5. 14 (SiMe), 12. 8 (SiCH2CH2CH2S), 13. 2 (BrCH2CH2CH2CH2Si), 14. 0 (CHJ (CH2) 12CH2CH2C02), 20. 1 (BrCH2CH2CH2CH2Si), 23. 9 (SiCH2CH2CH2S), 24. 9 (CH3 (CH2) 1OCH2CH2C02), 29. 3-29-9 (CH3 (CH2) 12CH2CH2C02), 30. 8 (SCH2CH2C02), 31. 9 (BrCH2CH2CH2CH2Si), 33. 44 20 (BrCH2CH2CH2CH2Si), 34. 2 (CH3 (CH2) 12CH2CH2C02), 36. 2 (SiCH2CH2CH2S), 63. 2 (SCH2CH2COO), 173. 5 (CH3CH2CH2 (CH2) 1OCH2CH2C02).  Anal.  Calc.  for C47H93Br04S2Si (894. 35 g / mol)%: C, 63. 12, H, 10. 48, S, 7. 17.  Exp.  %: C, 65. 15, H, 9. 95, S, 6. 35  o ~ o / l- (CH2) 14Me I ~ S B ~ Si r ~ s ~ Of ((CH2) 14Me O 25 HOCsH40G1A2.  BrG1A2 (1 is added in a vial under an inert atmosphere). 0 g, 3. 83 mmol), 1, 4- (OH) 2C6H4 (4. 21 g, 38. 3 mmol), K2C03 (1. 05 g, 7. 66 mmol), crown ether 18-C-6 (0. 10 g, 0. 38 mmol) and acetone (50 mL).  The mixture is stirred at 90 ° C for 24 hours.  The solvent is evaporated and the reaction crude is extracted with CH2CI2 and a saturated solution of NH4CI in water (50 mL).  The organic phase is dried over MgSO4 and then with Si02 for 30 minutes.  The solution is filtered through Celite and the solvent is evaporated.  The product 26The obtained is purified using a size exclusion chromatographic column (Bio-Beds S-X1) with THF as eluent thus obtaining HOC6H40Gl ~ as a brown oil with good yield (0. 9 g, 82%).  NMR (CDCiJ): 1HRMNO-0. 022 (s, 3 H, Si Me), 0. 57 (t, 2 H, CH2Si), 1. 43 (m, 2 H, CH2CH2Si), 1. 51 (d, 4H, SiCH2CH) 1. 75 (m, 2 H, 5 OCH2CH2), 3. 87 (t, 2 H, O CH2), 4. 83 (m, 4 H, SiCH2CHCH2), 5. 74 (m, 2 H, SiCHCH2), 6. 75 (m, 4 H, C6H402); NMR-13C (CDCiJ): 5. 9 (SiMe), 12. 6 (OCH2CH2CH2CH2Si), 20. 05 (OCH2CH2CH2CH2Si), 21. 1 (SiCH ~ CH2) 2S) 32. 9 (OCH2CH2CH2CH2Si), 68. 2 (OCH2), 115. 6 and 115. 9 (C6H402; CH), 113. 2 (SiCH2CHCH2), 134. 6 (SiCH2CHCH2), 149. 3 and 152. 9 (C6H402; CO).  Anal.  Cale.  For C17H2602Si (290.47 g / mol)%: C, 70. 29, H, 9. 02.  Exp.  %: C, 10 70. 15, H, 9. 95.  ~ I / Si ~ O - O-OH A2G10C6H40G1C3 (C02 (CH2) 14CH3) 2.  Following the procedure described for the above compound, the compound ~ Gl0C6H40G1C3 (C02 (CH2) 14CH3) 2 was obtained from 15 BrG1C3 (C02 (CH2) 14CH3) 2 (1. 0 g, 3. 44 mmol), HOC6H40G1A2 (3. 08 g, 3. 44 mmol), K2C03 (1. 00 g, 6. 89 mmol) and crown ether 18-C-6 (0. 10 g, 0. 34 mmol) as a yellow oil with good yield (3. 5 g, 92%).  NMR (CDCiJ): 1HRMN OR -0. 08 (m, 6H, SiMe), 0. 59 (m, 8H, OCH2CH2CH2CH2Si, SiCH ~ CH2) 2S), 0. 87 (m, 6H, CH3 (CH2) 14C02), 1. 24 (s, 52H, CH3 (CH2h ~ CH2hC02, OCH2CH2CH2CH2Si), 1. 54 (d, 4H, SiCH2CHCH2) 1. 58 (m, 8H, 20 CH3 (CH2), 2CH2CH2C02, SiCH2CH2CH2S), 1. 75 (m, 4H, OCH2CH2CH2CH2Si, CH3 (CH2) 10CH2CH2C02), 2. 29 (t, 4H, CH3 (CH2) 12CH2CH2C02), 2. 54 (t, 4H, SiCH2CH2CH2S), 2. 70 (t, 4H, SCH2CH2C02), 3. 80 (m, 4H, OCH2CH2CH2CH2Si), 4. 20 (t, 4H, SCH2CH2C02), 4. 83 (m, 4 H, SiCH2CHCH2), 5. 74 (m, 2 H, SiCHCH2), 6. 80 (m, 4 H, C6H402).  NMR-13C (CDCiJ) O -5. 14 (SiMe), 12. 8 (SiCH2CH2CH2S), 13. 2 (OCH2CH2CH2CH2Si), 14. 0 25 (CHJ (CH2) 12CH2CH2C02), 20. 1 (OCH2CH2CH2CH2Si), 23. 9 (SiCH2CH2CH2S), 24. 9 (CH3 (CH2) 10CH2CH2C02), 29. 3-29-9 (CH3 (CH2) 12CH2CH2C02), 30. 8 (SCH2CH2C02), 31. 9 (OCH2CH2CH2CH2Si), 33. 44 OCH2CH2CH2CH2Yes), 34. 2 (CH3 (CH2) 12CH2CH2C02), 36. 2 (SiCH2CH2CH ~), 63. 2 (SCH2CH2COO), 173. 5 (CH3CH2CH2 (CH2) 10CH2CH2C02), 115. 3 (C6H402; CH), 113. 2 (SiCH2CHCH2), 134. 6 (SiCH2CHCH2), 152. 9 (C6H402; CO).  Anal.  30 Calculated for C64H11806S2Si2 (1103.19 g / mol)%: C, 69. 63, H, 10. 77, S, 5. 81.  Exp.  %: C, 68. 15, H, 10. 90, S, 4. 30  27o. . . A- ~ I s ~ o (CH2h4Me ~ Si ~ 0-o- 'O ~ Si ~, f "- ~ S" vO-y (CH2) 14Me O (S03) 2C3G10CsH40G1C3 (C02 (CH2) 14CH3) 2.  The previous compound (0. 30 g, 0. 27 mmol), dissolved in a THF / MeOH mixture (75:25) and added to a solution of sodium 3-mercapto-1-propanesulfonate (0. 10 g, 0. 6 mmol) previously prepared in 5 ml of water.  5 On this final mixture is added in 4 portions, one every hour, the OMPA photoinitiator (0. 002 g, 0. 007 mmol).  The mixture is deoxygenated and irradiated with UV light each time.  The total reaction time was 4 hours.  The solvents evaporate and the reaction product is dissolved in distilled water and purified by ultrafiltration with cellulose membranes with a pore size between 500-1000 Da.  Finally, the water is removed in vacuo 10 And (S03) 2C3G10CsH40G1C3 (C02 (CH2) 14CH3) 2 is obtained as a white solid (0. 32 g, 82%).  NMR (020): 1HRMN ~ -0. 13 (m, 6H, SiMe), 0. 53 (m, 12H, OCH2CH2CH2CH2Si, SiCH2CH2CH2S), 0. 75 (m, 6H, CHJ (CH2) 14C02), 1. 15 (m, 52H, CH3 (CH2) 12 (CH2) 2C02, OCH2CH2CH2CH2Si), 1. 47 (m, 12H, CH3 (CH2) 12CH2CH2C02, SiCH2CH2CH2S), 1. 70 (m, 15 CH3 (CH2) 12CH2CH2C02), 2. 44 (m, 8H, SiCH2CH2CH2S), 2. 52 (m, 8H, SCH2CH2CH2S03, SCH2CH2C02), 2. 85 (m, 4H, SCH2CH2CH2S03), 3. 92 (m, 4H, OCH2CH2CH2CH2Si), 4. 30 (t, 4H, SCH2CH2C02), 6. 80 (m, 4 H, C6H402).  NMR-13c (020) ~ -5. 35 (SiMe), 12. 8 (SiCH2CH2CH2S), 13. 2 (OCH2CH2CH2CH2Si), 13. 92 (CHJ (CH2) 12CH2CH2C02), 20. 1 (OCH2CH2CH2CH2Si), 23. 9 (SiCH2CH2CH2S), 24. 5 (SCH2CH2CH2S03), 24. 9 20 (CH3 (CH2) 1OCH2CH2C02), 29. 3-29-9 (CH3 (CH2) ¡2CH2CH2C02), 30. 29 (SCH2CH2CH2S03), 32. 3 (OCH2CH2CH2CH2Si), 34. 1 (CH3 (CH2) 12CH2CH2C02), 35. 2 (SiCH2CH2CH2S), 50. 1 (SCH2CH2CH2S03), 63. 9 (OCH2CH2CH2CH2Si), 173. 3 (CH3CH2CH2 (CH2) 1OCH2CH2C02).  Anal.  Calculated for C70H132N20122012 Si2 (1460.33g / mol)%: C, 57. 57, H, 9. 11, S, 13. 17.  Exp.  %: C, 57. 45, H, 9. 65, S, 12. 35  25 28Example 5 - Formation of micelles from the compounds of the invention and determination of the critical micellar concentration.  For a micelle to form, there must be an appropriate hydrophilic-lipophilic balance within the compound to be analyzed.  In the compounds of the invention, the hydrophobic effect is a consequence of the dendritic skeleton and fatty acid, while the hydrophilic part is due to the external chain of type S- (CH2) and -R3 discussed above.  The formation of micelles from the dendrons of the invention is determined by the study of the critical micellar concentration (CMC).  For the study of said concentration there are 10 different methods, among which are conductivity, surface tension or fluorescence.  Conductivity measurements were made within a range of concentrations between 1x10-3 and 1x10-7M in a solvent such as water, but without ruling out others.  The addition of 15 ionic dendrons causes an increase in the number of transported charges and therefore an increase in conductivity.  When the CMC barrier is overcome, the load diffusion is much slower with respect to the initial situation since the micelles are larger than the mangroves and therefore the increase in conductivity is less significant (Table 1, Figures 8 and 9).  Conductivity measurements also determine the degree of ionization, observing that anionic systems have a higher degree of ionization than cationic systems.  Table 1.  CMC and degree of ionization of micelles obtained by conductivity for the compounds RC02GnC2 (NMe3 +) m (R = Me (CH2) 14, Me (CH2) 4; n = 1, m = 2; n = 2, m = 4, n 25 = 3, m = 8) and RC02G1 C3 (S03-) 2 (R = Me (CH2) 14, Me (CH2) 4; n = 1, m = 2; n = 2, m = 4, n = 3 , m = 8).  CMC (mM) Ionization R Gn S03-NMe / S03-NMe3 + Me (CH2) 4 G, ----------- Me (CH2) 4 G2 --- 0.32 0. 58 0.73 Me (CH2) 4 G3 0.10 0.12 0. 24 0.33 Me (CH2) 14 G1 0.24 0.12 0.69 0.37 Me (CH2) '4 G2 0.14 0.11 0.78 0.20 Me (CH2) 14 G3 0.14 0.19 0.79 0.49 29Surface tension is another technique commonly used to determine CMC.  The way to carry out studies of surface tension measurements is analogous to the conductivity determination.  The increase in the concentration of the compounds of the invention leads to a decrease in the surface tension of the solution with respect to the value 5 of the pure solvent (Figure 10).  The repulsion between charges at the head of the compounds of the invention directly affects CMC, and therefore the addition of electrolytes in aqueous solutions decreases said repulsion, which favors the formation of micelles.  The size of the counterions and the concentration of the electrolyte are essential to regulate the micellar formation.  10 Characterization of micelles.  Different techniques can be used for this process in micelles formed from the compounds of the invention, such as light scattering (DLS) and 15 l potential, but without ruling out others.  By means of the DLS study, the hydrodynamic radius is obtained, which in the micelles of the invention showed to be independent of the concentration above the CMC.  As the dendron generation increases, the hydrodynamic radius decreases.  The potential 1 shows that once the micelle has been formed from the compounds of the invention, the value is approximately -61 mV (anionic systems), thus indicating the formation of stable systems.  25 STUDY OF THE INTERACTION OF MICELLES WITH DRUGS The use of micellar systems as means of transport of drugs and nucleic acids, among other molecules of interest, is becoming stronger every day in the field of biomedicine.  As an example of a drug, procaine hydrochloride (HCP, Figure 11), known local anesthetic, has been used.  Due to the cationic nature of this drug, micelles obtained from the anionic compounds of the invention have been used.  Absorbance measures are used to calculate a partition coefficient and establish the encapsulation capacity.  The concentration of HCP remains constant and the concentration of the 30 is variedcompounds of the invention.  Below CMC, the absorbance produced by the effect of the drug has no significant changes.  When this concentration is exceeded, a gradual increase of 5 absorbance added to a shift thereof is observed towards greater wavelengths, characteristic behavior of substances that rapidly change the polarity of the environment from a polar medium to a less polar one (inside of the micelle).  The calculated partition coefficient allows us to conclude that these micelles have a greater capacity to encapsulate the drug than other ionic surfactants such as SDS or CTAB (R.  Hosseinzadeh, 10M.  Gheshlagi, et al.  Cent.  Eur.  J.  Chem 2009, 7, 90).  This study reveals the ability of micelles formed by dendrons carbosilane and fatty acids at the focal point to transport drugs.  The location of the drug, electrostatic interaction outside, internalization between units of the micelle, or encapsulation by the micelle, depends on the type of drug and the medium: aqueous saline or non-saline or organic medium.  For example, in the case of procaine in non-saline aqueous medium with micelles formed by dendrons of type RC02GnC3 (SOf) m (R = Me (CH2) 14), this is located on the micellar surface interacting electrostatically with the charges of the dendrons  20 BIOLOGICAL ACTIVITY OF CATIÓNIC SYSTEMS AGAINST BACTERIA The antibacterial capacity of cationic systems against Gram + type bacteria has been studied (eg.  S.  aureus) and Gram- (ex.  AND.  eoll)  The main difference between these 25 bacteria lies in the constitution of the bacterial membrane.  However, its activity against other bacteria and other microorganisms such as amoebas and other parasites is not ruled out.  30 35 MATERIALS AND METHODS Dendrons.  As an example, the data corresponding to the compounds RC02GnC2 (NMe3 +) m (R = Me (CH2) n; n = 4, 14) are presented.  31Assessment of the antibacterial capacity of the compounds.  The minimum inhibitory concentration (MIC) of the compounds is determined in 96-well microplates, using the standard ISO 20776-1 method.  The test is carried out for 5 sextuplicates for each concentration analyzed.  For the tests the bacteria Escherichia coli (CECT 515, Gram negative) and Staphylococcus aureus (CECT, 240 Gram positive) were used.  Both strains were obtained from the "Spanish Type Culture Collection" (CECT).  A stock solution is prepared by dissolving 0.01024 g of the compound under study in 10 ml of distilled water (1024 ppm).  After that, sterile distilled water is added until the desired concentrations are obtained.  100 ~ L of the solution with the desired concentration is added to each well of the microplates and it is completed with 100 ~ L of MuellerHinton broth (Scharlau, ref.  02-136) double concentrate of what is indicated for its preparation.  Finally, 5 ~ L of a bacterial solution of 2 x 107 CFU / mL is added.  The microplates are incubated at 37 ° C for 24 hours using a 15 ELX808iu microplate reader (Bio-Tek Instruments).  The minimum bactericidal concentration (CMB) is the smallest concentration of the compound that does not allow bacterial growth.  This CMB is calculated by inoculating 5 ~ 1 of each of the wells of the microplate used for the calculation of MIC, in a Petri dish 20 with Mueller-Hinton agar (ref.  02-136, Scharlau).  After 48 h of incubation at 37 ° C, the presence of colonies is analyzed.  Results  The antibacterial capacity (Table 2) of the compounds of the invention studied depends on the generation, length of the fatty acid chain and type of bacteria.  The best results are obtained for generation two and for chains such as hexanoic acid at the focal point.  325 Table 2.  Antibacterial activity of the compounds RC02GnC2 (NMe3 +) m (R = Me (CH2) 14, Me (CH2) 4; n = 1, m = 2; n = 2, m = 4, n = 3, m = 8).  S.  Aureus E.  Cabbage; Compound CMI CMB CMI CMB Me (CH2) 14C02G1 (NMe3 +) 2 16 16 32 64 Me (CH2) 14C02G2 (NMe3 +) 4 8 16 32 32 Me (CH2) 14C02G3 (N Me3 +) 8 8 8 8 16 Me (CH2 ) 4C02G1 (NMe3 +) 2 16 16 16 32 Me (CH2) 4C02G2 (NMe3 +) 4 0.5 1 1 1 Me (CH2) 4C02G3 (N Me3 +) 8 4 4 8 8 BIOLOGICAL ACTIVITY OF ANIONIC SYSTEMS AS ANTIVIRAL AGENTS AGAINST HIV.  Anionic systems whose functional groups interact with the gp120 protein of the human immunodeficiency virus type 1 (HIV-1), the CD4 cell receptor and / or the CCR5 or CXCR4 co-receptors, acting in the early stages of the viral cycle have been studied inhibiting HIV infection, as well as in herpes virus type 2 (HSV-2), as they also appear to bind in the early stages of the viral cycle.  The study of these two viruses is due to the fact that both cause infectious diseases through sexual transmission and that the probability of becoming infected with HIV by people infected with HSV-2 is three times greater than those who are not infected by this virus.  MATERIALS AND METHODS 20 Dendrones.  Six polyanionic carbosilane dendrons were screened, RC02GnC3 (SOf) m (R = Me (CH2k n = 1, m = 2, referred to below as BDCG044; n = 2, m = 4, 335 referred to below as BOCG046; n = 3, m = 8, referred to below as BOCG048; R = Me (CH2) 14, n = 1, m = 2, referred to below as BOCG050; n = 2, m = 4, referred to below as BOCG052; n = 3, m = 8, referred to below as BOCG054).  Reagents  As a negative control and cell death control, dimethylsulfoxide (OMSO, Sigma-Aldrich) was used for cell toxicity tests.  The antiretroviral T-20 (Genetech, San Francisco, Ca, USA) was used as a control for the inhibition of viral replication. UU. ), an inhibitor of HIV-1 fusion to target cells due to its binding to the gp41 glycoprotein of the virus.  Tenofovir (TFV, Gilead Sciences, Foster City, CA, USA) as a transcriptase inhibitor and raltegravir (RAL, Merck Sharp & Oohme Corp, Whitehouse Station, NJ, USA) as a retrotransciptase inhibitor.  Nuclease-free water (Promega) 15 was used to obtain the working dilutions of the compounds from the stock and the PBS (Lonza, MO, USA) to wash the plates in the different experiments.  Cells.  20 TZM bl (ATCC® PTA-5659 ™), a cell line from a HeLa line generated from the JC53-bl line, which expresses the markers C04, CCR5 and CXCR4, and the luciferase and 3-galactosidase genes under the HIV-1 promoter control.  They were obtained through the NIH AIOS Research and Reference Reagent Program. They were grown in OMEM culture medium (Life technology, Madrid, Spain) supplemented with 5% SFB inactivated by heat, 2 mM L-glutamine and the antibiotic cocktail mentioned above at 37 ° C in an atmosphere of 5% C02.  Viral isolated.  The viral isolates R5 tropic HIV-1NLAD8 and X4 tropic HIV-1NL4. 3, are isolated from 30 laboratories from the NIH AIOS Research and Reference Reagent Program, Oivision of AIOS, NIAIO.  The infectivity of HIV-1 viral isolates was quantified in the TZM cell line. bl.  2x1 04 of TZM-bl cells were cultured with complete culture medium in 96-well plates and HIV-1 isolates were added at different concentrations for 3 hours, after this time the cells were washed twice with sterile PBS and left in culture medium.  3. 4After 48 hours post-infection the percentage of infection was determined by the luminescence measurement (Luciferase Assay System, Promega) using a plate reader (Synergy 4 Plate Multilector, Biotek Instrument).  5 Toxicity test by reduction of tetrazolium salts or MIT.  This technique is a colorimetric assay based on the selective ability of living cells to reduce 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide in formazan insoluble crystals.  This method allows to determine the lethal effect of the compounds 10 under study, in this case the polyanionic carbosilane dendrons, on the cellular metabolism, since the cellular damages translate into a decrease of the mitochondrial activity of the cell, being able to measure the cytotoxicity of these molecules  This test was carried out according to the manufacturer's instructions (MTT, Sigma-Aldrich, St Louis, USA. UU. ).  Briefly, after the incubation time of the different populations, 15 cells in a flat-bottom 96-well plate (15x103 TZM cells. bl / well) with the different selected concentrations of the nanoparticles, the supernatant containing the nanoparticle was removed and replaced by 200IJL of Opti-MEM® (medium without serum or phenol red) and 20 IJL of MTT (Tiazolil Blue, 5 mg / mL, final well concentration of 0.5 mg MTT / mL) per well.  After 2 hours of incubation under culture conditions, the plate was centrifuged at 1500 r. p. m.  10 min and the subsequent removal of the supernatant with excess MTT that did not react.  Formazan crystals were dissolved in 200 IJL of DMSO.  The plate was stirred at 700 r. p. m.  to ensure the correct dissolution of said crystals and the formazan concentration was determined by spectrophotometry using a plate reader (Synergy 4 Plate Multilector, Biotek 25 Instrument) at a wavelength of 570 nm (reference 690 nm).  The spectrophotometer was calibrated to O using Opti-MEM® without cells.  The relative cell viability (%) with respect to the control (untreated cells) was calculated based on the formula: [A] test / [A] control x 100.  20% DMSO was used and was used as a positive toxicity control.  Each experiment was performed in triplicate.  30 Test of inhibition of anionic systems: quantification of HIV-1.  The inhibition capacity of HIV-1 infection of anionic systems in TZM was determined. bl.  For this, the different cell populations were pre-treated with the 35 different concentrations of the maximum non-toxic compounds of interest in 35 plate96 flat bottom wells (15x103 TZM cells. bl / well) for 1 hour under culture conditions.  The cells were subsequently infected with 20 ng HIV / 106 TZM. bl of the viral isolates R5 tropic HIV-1NLAD8 and X4 tropic HIV-1NL4. 3, for 3 hours.  Next, the supernatant containing the excess dendrons and viruses was removed, and two washes were performed with 200 IJL of PBS, then replaced with 200 IJL of fresh medium maintaining the cultures for 48 h.  After this post-infection time, the supernatant was removed, followed by a wash with PJ 2001J1, to proceed to lyse the cells by adding 501J1 lysis buffer (Promega) per well for 30 min at 4 ° C.  Subsequently, the cells were centrifuged at 1500 r. p. m.  10 for 5 min to precipitate cell debris, and 20 IJI were collected from the cell lysate.  15 This volume was transferred to a reading plate and 60 IJI / luciferase substrate well (Luciferase Assay System, Promega) was added to determine the percentage of infection by measuring luminescence using a plate reader (Synergy 4 Plate Multilector , Biotek Instrument).  Each experiment was carried out in triplicate.  Test of inhibition curves and calculation of leso The inhibition curves of HIV-1 infection of the anionic systems in the TZM cell line were determined. bl (Figure 14).  Cells were treated with different non-toxic concentrations of the compounds of interest (0.001-10 IJM in TZM. bl) in flat-bottom 96-well plates (15x1 03 cells / well).  The cells were incubated with the treatments for 1 hour under culture conditions and then the cells were infected with 20 ng HIV-1/106 TZM. bl, with both R5 and X4 viral isolates for 3 hours, under culture conditions.  The supernatant containing the excess of dendrons 25 and viruses was removed, and consecutive washes were performed with 200 IJL of PBS and, finally, replaced with 200IJL of fresh medium maintaining the cultures for 48 hours.  After this time, the same procedure detailed above was performed to quantify HIV-1 infection.  Each experiment was carried out in triplicate.  Subsequently, to calculate the IC5o values, the CalcuSyn software (Biosoft, 30 Cambridge, UK) was used.  Addition time test In order to determine at what point in the HIV-1 viral cycle the 35 dendrons are acting, addition time assays were performed on the TZM cell line. bl (Figure 36fifteen).  15x103 TZM were plated. bl / well in 96 well plates.  They were allowed to incubate 24 hours under culture conditions so that the cells adhered to the plate.  Subsequently, TZM cells were infected. bl with the R5 HIV-1NLAD8 viral isolate (20 ng HIV / 106 TZM. bl).  The cells were treated with the dendrons with the maximum non-toxic concentration, as well as the drugs used as controls, at different times post-infection (O, 1, 2-7 h).  They were allowed to incubate 48 hours under culture conditions, and subsequently the infection was quantified as described above.  T-20, Tenofovir (TFV) and Raltegravir (RAL) were used as controls.  Each experiment was carried out in triplicate.  10 Results.  In the TZM cell line. bl (Figure 12) concentrations of anionic systems in a range of 0.1 to 50 J. were studied. lM.  Maximum non-toxic concentrations were obtained for use in subsequent trials.  These concentrations were: BDCG044: 15 1 J. lM; BDCG046: 1 J. lM; BDCG048: 10J. lM; BDCG050: 0.1 J. lM; BDCG052: 0.1 J. lM; BDCG054: 10 J. lM.  Compounds BDCG044, BDCG046, BDCG050 and BDCG052 do not show antiviral activity against both HIV viral isolates, so these 20 compounds were discarded (Figure 13).  Compound BDCG048 manages to inhibit 98.5% infection in both HIV viral isolates, while compound BDCG054 inhibits infection by the R5 HIV-1NLAD viral isolate by 99.1%, and the HIV-1NL4 X4 viral isolate. 3in more than 99.9.  Taking these results into account, we carry out subsequent tests using compounds with a potent antiviral activity: BDCG048 and BDCG054.  25 The inhibition curves obtained (Figure 14) show in all cases a dose-dependent behavior, since as the dendron concentration increases, greater viral inhibition is observed.  In the viral isolate R5 HIV-1NLAD8 It is observed that at a concentration of both dendrons of 5 J. lM, an inhibition of more than 30 is achieved by 90% (Figure 14A)).  In the viral isolate X4 HIV-1NL4. 3, 100% inhibition rates are reached from 1 J. lM in both dendrons, so dendrons are more effective against the viral isolate X4 HIV-1NL4. 3que versus R5 HIV-1NLAD8.  Table 3 shows the ICso values obtained: 37Table 3.  IC50 values for the BDCG048 and BDCG054 dendrons in both HIV-1 viral isolates.  R5-H IV -1 NLAD8 X4-HIV-1 NL4. 3 IC50 (IJM) BDCG048 0.1046 0.0351 IC50 (IJM) BDCG054 0.0534 0.0073 In the data shown in Figure 15, it is observed that the BDCG048 and 5 BDCG054 dendrons are capable of inhibiting infection of the HIV-1 at short times post-infection (0-1 h) And as time goes by this capacity for viral inhibition decreases, so it can be said that dendrons are acting in the early stages of infection.  38 

权利要求:
Claims (1)
[1]
CLAIMS 1. Dendron of a carbosilane nature that contains an outer layer (1) and a focal point 5 (11) comprising: 10 15 20 25 -The outer layer or periphery that it consists of. Totally or partially. in the same or different units from the group of formula (1): -Si-fR2) I P (R1) 3-p (1) where: R1 is a (C1-C4) alkyl group. preferably R1 is a methyl group; p is an integer and ranges from 1 to 3. preferably p is 2; and R2 is the following group - (CH2) x-S- (CH2) y-R3; x represents an integer between 2 and 5; preferably x is 2 or 3; y represents an integer ranging from 1 to 10; preferably y ranges from 1 to 5; more preferably y is 1,2 or 3; R3 is a -OH group. -S03H. -OS03H. -COOR 'or -NR .. R · ... where R'. R "YR .. •. Independently represent an alkyl group (C1-C4) or a hydrogen, or any of its salts. -The focal point that can be selected from the group of formula (11): where: z is a An integer ranging from 1 to 10. preferably z ranges from 1 to 5 and more preferably z is 3 or 4, and is an atom or group of atoms that acts as a link between the dendritic wedge and the fatty acid or its derivative. Y = O. NH.S; R5 is the substituent chain of the fatty acid (R5C02H) or its derivative, preferably R5 = Me (CH2) a. A is an integer ranging from O to 30. This group (11) is It is attached to the dendritic structure or the periphery through a Si atom. 2. Compound according to the preceding claim, where the fatty acid derivative (R5) is saturated straight chain and contains between 4 and 20 carbon atoms. main chain having branches, preferably it is a derivative of palmitic acid.5 caproic or oleic, without ruling out others. 3. Compound according to any one of the preceding claims, wherein R3 is a group -N (CH3) 2 or an ammonium group -N (CH3 +) 3. 4. Compound according to any one of claims 1 to 2, wherein R3 is a -C02H or -C02Me group, or any of their salts. 5. Compound according to any one of claims 1 to 2, wherein R3 is a group -S03H or -OS03H, or any of their salts. 6. Process for obtaining the compounds described according to any of claims 1 to 5, comprising a reaction between the fatty acid and a carbosilane dendritic wedge, but also presenting a focal point of the type - (CH2) xZ (Z = CI , 15 Sr, I), and the corresponding functional groups in the periphery. Said reaction is preferably carried out, but without ruling out others, in a polar solvent such as DMF, DMSO, acetone, THF, acetonitrile or combinations thereof, preferably in the presence of base. 7. Process for obtaining the compounds described according to any of claims 1-5, comprising a reaction between the fatty acid and a dendritic wedge but also having a focal point of the type - (CH2) xA (A = OH, NH2, SH), and the corresponding functional groups in the periphery. Said reaction is preferably carried out in a polar solvent such as DMF, DMSO, acetone, THF, acetonitrile, others or combinations thereof, preferably in the presence of base and coupling agents, such as carbodiimide derivatives, but without ruling out others. 8. Process for obtaining the compounds described according to any of claims 1 to 5, comprising a thiol-ene addition reaction between a dendritic wedge, which has the fatty acid at the focal point but terminal olefin functions at the periphery, and a thiol of the HS (CH2) yR3 type, where R3 and y have been defined in claims 1-5. Said reaction is preferably carried out in a polar solvent such as DMF, DMSO, acetone, THF, acetonitrile, alcohols or water or others or combinations thereof, preferably by UV irradiation in the presence of photoinitiators or by heating in the presence of radical initiators. 409. Janus-type carbosilane dendrimer formed by two units derived from carbosilane dendrons. One of them is a peripherally functionalized dendron according to claims 1 to 5 and the other unit is of the carbosilane type with an outer layer or periphery comprising, totally or partially, the same or different units from the group of formula (IV): 10 15 20 25 30 (IV) where: R 'is a (C, -C4) alkyl group, preferably R' is a methyl group; p is an integer and ranges from 1 to 3, preferably p is 2; and R7 is the following group - (CH2) x-S- (CH2) y-Y-C (O) R5; x represents an integer between 2 and 5; preferably x is 2 or 3; y represents an integer between 1 and 10; preferably y ranges from 1 to 5; C (O) R5 represents a fatty acid or its derivative, as defined above for R5 and Y. The union between the two units of the Janus-type dendrimer is selected from the group - (CH2) c-R8- (CH2) C ', where: c and c' are an integer ranging from 1 to 10, preferably ranging from 1 to 5 and more preferably 3 or 4; furthermore c and c 'may or may not be equal to each other; R8 is any type of linkage, preferably of the -OR90- type; where R9 is any hydrocarbon group, preferably R9 is an aromatic group of the CSH4 type. 10. Procedure for obtaining Janus-type dendrimers, according to claim 9, characterized by the coupling of each wedge to the R8 group. This coupling can be done in any order. 11. Procedure for obtaining Janus-type dendrimers, according to claim 9, characterized by introducing a wedge with the fatty acid functions in the periphery and another with olefin groups. The order of introduction of the wedges is indistinct. From 41Janus dendrimer containing olefin functions, the compounds of the invention are obtained through a thiol-ene reaction with a thiol derivative containing the anionic or cationic group, or a precursor thereof. 5 12. Process for the formation of micelles with a carbosilane dendritic wedge according to claims 1 to 5. Preferably the fatty acid (R5C02H) is saturated straight chain, but without ruling out other chains, and contains between 4 and 20 carbon atoms, being able to branching the main chain. Preferably, it is a derivative of palmitic acid (R5 = Me (CH2) 14), caproic (R5 = Me (CH2) 4), without ruling out others. 13. Process for forming micelles with Janus-type dendrimers according to claim 9. 14. Process for forming micelles with a wedge or carbosilane dendrimer, according to 15 claims 1 to 9, in the presence of other compounds such as sterols, preferably in the presence cholesterol. Micellar formation according to any one of claims 12 to 14 in the presence of a drug. 16. Micelle formation according to the preceding claim, wherein the drug is a compound with antibiotic, antiviral, anti-inflammatory, anti-cancer or other properties. 17. Use of the dendritic and / or micellar systems described according to any of the preceding claims, as an antibacterial, amebicidal or antiparasitic agent. 18. Use of the dendritic and / or micellar systems described according to any of claims 1 to 16, as an antiviral agent. 19. Use according to the preceding claim, wherein the virus is the human immunodeficiency virus (HIV) or the herpex simplex virus (HSV). 20. Use of the cationic dendritic and / or micellar systems described according to any one of claims 1 to 16, as a non-viral vector. 4221. Use according to the preceding claim, where the non-viral vector is used for the transfection or internalization of nucleic material, preferably the nucleic material is selected from oligonucleotides, siRNA or DNA. 22. Use of the dendritic and / or micellar systems described according to any of claims 1 to 16, for the manufacture of a medicine. 23. Use of the dendritic and / or micellar systems described according to any of claims 1 to 16, for the manufacture of a medicament for the prevention and / or treatment of diseases caused by a microorganism. 24. Use according to the preceding claim, wherein the disease is caused by a bacterial or parasitic infection. 25. Use of the dendritic and / or micellar systems described according to any of claims 1 to 16, for the manufacture of a drug for the prevention and / or treatment of diseases caused by HIV or HSV. 26. Pharmaceutical composition comprising a dendritic and / or micellar system according to any one of claims 1 to 16. 27. Pharmaceutical composition according to the preceding claim, further comprising a pharmaceutically acceptable carrier and / or other active principle, preferably an antibiotic, anti-inflammatory or antiviral. 28. Pharmaceutical composition according to any of claims 26 and / or 27, further comprising nucleic material. The nucleic material is preferably selected from oligonucleotides, RNA or DNA. 29. Use of the dendritic and / or micellar system according to any of claims 1 to 16, as a transport vehicle for molecules. 30. Use according to the preceding claim, wherein the molecule is a drug, preferably with antibiotic, antiviral or anticancer properties, but without ruling out others. 43

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ES2365685A1|2010-03-25|2011-10-10|Universidad de Alcalá de Henares|Carbosilan dendrimers with a polyphenolic nucleus and its use as antivirals. |

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ES2444490A1|2012-07-25|2014-02-25|Universidad De Alcalá|Homo- and hetero-functionalised carbosilane dendritic compounds|

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