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Keywords:

Anti-HIV Agents, Cell Line, HIV-1, HIV-2, Humans, Molecular Structure, Thiazoles, Virus Replication, Disulfides, 0304 Medicinal and Biomolecular Chemistry, 0601 Biochemistry and Cell Biology, 1117 Public Health and Health Services, Virology, 3404 Medicinal and biomolecular chemistry

Abstract:

A series of 3,4,5-trisubstituted isothiazoles has been screened against HIV-1 (IIIB) and HIV-2 (ROD) at sub-toxic concentrations in acutely infected MT-4 cells. Among the tested compounds, only 3-mercapto-5-phenyl-4-isothiazolecarbonitrile was found to inhibit the replication of HIV-1 (IIIB) and HIV-2 (ROD) at 50% effective concentrations (EC50) of 7.8 and 9.7 microg/ml, respectively. The presence of a thioalkyl chain or dialkylamino function in the 3-position caused a loss of anti-HIV activity. New 4-cyano-5-phenylisothiazoles with other substituents in the 3-position have also been synthesized and studied as potential anti-HIV agents. Our results have demonstrated that 5-phenyl-3-(4-cyano-5-phenylisothiazol-3-yl) disulphanyl-4-isothiazolecarbonitrile and S-(4-cyano-5-phenylisothiazol-3-yl)-O-ethyl thiocarbonate are effective against both HIV-1 (IIIB) (EC50=13.6 and 15.2 microg/ml, respectively) and HIV-2 (ROD) (EC50=17.4 and 13.4 microg/ml, respectively).