Recently, antimicrobial peptides (AMPs), also called host defence peptides (HDPs), are attracting great interest, as they are a highly viable alternative in the search of new approaches to the resistance presented by bacteria against antibiotics in infectious diseases. However, due to their nature, they present a series of disadvantages such as low bioavailability, easy degradability by proteases, or low solubility, among others, which limits their use as antimicrobial agents. For all these reasons, the use of vehicles for the delivery of AMPs, such as polymers, nanoparticles, micelles, carbon nanotubes, dendrimers, and other types of systems, allows the use of AMPs as a real alternative to treatment with antibiotics.
Cationic carbosilane dendrimers of generations 1–3 have been synthesized employing thiol–ene click chemistry. The obtained dendrimers present three different types of ammonium functions, two of them with the charge at the surface, –NH3+ and –NMe3+, and other with the charge internalized by the presence of ethylalcohol moieties, –[NMe2(CH2CH2OH)]+. The influence of –NMe3+ and –[NMe2(CH2CH2OH)]+ in dendrimer structure have been studied by molecular dynamics. The antibacterial properties of these families of dendrimers have been evaluated against Gram-positive (Staphylococcus aureus CECT 240) and Gram-negative (Escherichia coli CECT 515) bacterial strains, and the results have been compared with those obtained for related cationic carbosilane dendrimers functionalized by hydrosilylation reactions. These data show the relevance of the sulfur atom versus the silicon atom close to the dendrimer surface and the outer charge versus the inner charge. Finally, the stability of the most active first generation dendrimers vs. pH and temperature has also been studied.
A new family of amine- and ammonium-terminated carbosilane dendrimers of the type Gn-[Si(CH2)3N(Et)CH2CH2NMe2]x and Gn-{[Si(CH2)3N+R(Et)CH2CH2N+RMe2]x(X−)y} (where n = 1, 2 and 3; R = H, X = Cl; R = Me, X = I) respectively has been synthesized by hydrosilylation of N,N-dimethyl-N′-allyl-N′-ethyl-ethylenediamine, [(CH2 CH–CH2)(Et)N(CH2)2NMe2] with the corresponding hydride-terminated dendrimers and subsequent quaternization with HCl or MeI. Quaternized dendrimers are soluble and stable in water or other protic solvents for long time periods. The antibacterial properties of the quaternary ammonium functionalized dendrimers have been evaluated showing that they act as potent biocides in which the multivalency along with the biopermeability of the carbosilane dendritic skeleton play an important role in the antibactericidal activity of these compounds.
In recent years innovative nanostructures are attracting increasing interest and, among them, dendrimers have shown several fields of application. Dendrimers can be designed and modified in plentiful ways giving rise to hundreds of different molecules with specific characteristics and functionalities. Biomedicine is probably the field where these molecules find extraordinary applicability, and this is probably due to their multi-valency and to the fact that several other chemicals can be coupled to them to obtain desired compounds. In this review we will describe the different production strategies and the tools and technologies for the study of their characteristics. Finally, we provide a panoramic overview of their applications to meet biomedical needs, especially their use as novel antimicrobials.
21 March 2006 in European Journal of Inorganic Chemistry