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02656 DESIGN OF ANTI-HIV MICROBICIDES WITH INCLUSION OF PHARMACOPHORE MODIFIERS AND PSEUDO-LIGANDS Timofeyev I. At present, the whole humanity can be considered as a risk group for AIDS. Radically efficient medicines which could allow curing HIV infection have not been created yet; available preparations only somewhat slow down the development of AIDS. On the basis of co-polymers of divinyl ether with maleic anhydride, polymeric matrixes modified with hydrophobic pharmacophores and peptide imitators of pseudo-ligands of HIV-1/2 coreceptors have been synthesized. It was demonstrated previously that the prototypic preparations (like Amant) are membrane-acting compounds exhibiting a clearly expressed antiviral effect toward shell viruses (influenza, parainfluenza, respiratory syncytial virus etc.). By evaluating the newly synthesized complex membrane-acting compounds in vitro, their low toxicity was revealed (CC50>1,5mg/ml) for human lymphocitic cells (MT-4, PBMC), as well as high anti-HIV activity (by means of viral procedure: suppression of reproduction of virus [EC50], and by means of ELISA [IC50] measuring inhibition of the production of ?24 HIV-1 protein), which was 1-30mg/ml upon the culture of permissive cells (MT-4), infected with different strains of HIV-1, and upon PBMC under infection with R5 and X4 tropic strains of HIV-1. Maximal level of antiviral efficiency was revealed when preparations were introduced at the stage of virus adsorption and were during the whole of cultivation. From our point of view, these compounds can be promising for the development of microbicid preparations. Questions concerning the development of optimal means of transporting the complex microbicide compounds of this class are under investigation. Dr. Igor Timofeyev |
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