Polyanion inhibitors of human immunodeficiency virus and other viruses. 1. Polymerized anionic surfactants.

A series of polyanionic compounds was synthesized and evaluated for their activity against human immunodeficiency virus (HIV-1, HIV-2) and various other RNA and DNA viruses. Several compounds, i.e., 2p, 3p, 8p, 13p, 14p, 15p, 17p, 18p, and 19p, proved active against HIV-1 within the concentration range of 0.1-3 micrograms/mL while not being toxic to the host cells (CEM, MT-4) at concentrations up to 100 micrograms/mL or higher. As a rule, these polyanionic compounds proved also active, albeit at somewhat higher concentrations than those required for HIV-1 inhibition, against a number of other enveloped viruses, including HIV-2, human cytomegalovirus, influenza A virus, respiratory syncytial virus, and arenaviruses (Junin and Tacaribe). Among the most potent HIV-1 inhibitors ranked compounds 18p and 19p, the sodium salts of N-methylamides obtained by polymerization of monomers prepared starting from 10-undecenoyl chloride and omega-aminoalkanoic acids.

Polyanion inhibitors of human immunodeficiency virus and other viruses. 5. Telomerized anionic surfactants derived from amino acids.

omega-Acryloyl anionic surfactants, whose polar heads are derived from amino acids, have been telomerized to prepare polyanions of a predetermined molecular weight. The main goal of this study was to verify whether the antiviral activity is influenced by the degree of polymerization of the polyanions. The oligomeric polyanions were evaluated for their activity against human immunodeficiency virus (HIV-1 or HIV-2) and various other RNA and DNA viruses. With regard to their anti-HIV activity, a minimum number of anionic groups was necessary to achieve an inhibitory effect. Moreover, to be active the overall conformation of the polyanion must be such that the anionic groups are located on the external site of the molecule. With some of the polyanions, a 50% inhibition concentration (IC50) as low as 1 microgram/ mL, or even 0.1 microgram/mL, was noted against HIV-1 in CEM-4 and MT-4 cells, respectively. The most potent polyanions also proved active against human cytomegalovirus and herpex simplex virus at concentrations of 5-10 and 20-40 micrograms/mL, respectively. No activity was observed against any of the other viruses tested (i.e., vesicular stomatitis, Sindbis, Semliki forest, parainfluenza, Junin, Tacaribe, Coxsackie, polio, reo, and vaccinia). No toxicity for the host cells was observed at concentrations up to 200 micrograms/mL.

Polyanion inhibitors of human immunodeficiency virus and other viruses. 6. Micelle-like anti-HIV polyanionic compounds based on a carbohydrate core.

A new class of polyanionic compounds, inhibitors of human immunodeficiency virus, was obtained from radical addition of mercapto acid or mercapto ester on a perallylated carbohydrate under UV irradiation with a catalytic amount of AIBN. Unlike the polyanions that we have previously prepared by polymerization reactions, the compounds are structurally well defined. Polyanions bearing 16 carboxylate groups showed a 50% inhibitory concentration (IC50) of 0.1-4.1 micrograms/mL against HIV-1 in MT-4 cells while not being toxic to the host cells at concentrations up to 125 micrograms/mL. The most potent polyanions also proved active against human cytomegalovirus at concentrations of 1-14 micrograms/mL. No activity was observed against any of the other viruses tested (i.e., herpes simplex virus, vesicular stomatitis virus, Sindbis, Semliki forest, parainfluenza-3, Junin, Tacaribe, Coxsackie B4, polio-1, reo-1, or vaccinia virus).