3-(5-Dimethylamino-1-naphthalenesulphonyl)-2-(3-pyridyl)thiazolidine (YHI-1) selectively inhibits human immunodeficiency virus type 1.

Abstract

3-(5-Dimethylamino-1-naphthalenesulphonyl)-2-(3-pyridyl)thiazolidi ne (YHI-1), a synthetic analogue of D-cysteinolic acid isolated from sardines (Sardinops melanostictus), was found to be a specific inhibitor of human immunodeficiency virus type 1 (HIV-1) replication in various cell cultures. YHI-1 inhibited HIV-1IIIB replication with a 50% effective concentration (EC50) of 3.35, 10.23 and 4.61 microM in MT-4 cells, peripheral blood mononuclear cells and MAGI-CCR5 cells, respectively. However, no antiviral activity was observed with non-nucleoside reverse transcriptase inhibitor (NNRTI)-resistant HIV-1 strains, such as nevirapine-resistant HIV-1HE/NEV and MKC-442-resistant HIV-1IIIB-R, or with HIV-2ROD or SIVMAC. YHI-1 failed to inhibit reverse transcriptase (RT) activity in vitro with different template-primer systems. Time-of-addition experiments, the failure to inhibit NNRTI-resistant strains and the failure to show in vitro activity against RT suggest that a metabolite of YHI-1 inside the cell acts like an NNRTI. Thus, YHI-1 seems to belong to a new class of HIV-1 inhibitor and is a good candidate for further development.