Both 2',3'-dideoxythymidine and its 2',3'-unsaturated derivative (2',3'-dideoxythymidinene) are potent and selective inhibitors of human immunodeficiency virus replication in vitro

Abstract

2',3'-Dideoxythymidine (ddThd) and its 2',3'-unsaturated derivative 2',3'-dideoxythymidinene (ddeThd) are potent and selective inhibitors of human immunodeficiency virus (HIV) in vitro. When evaluated for their inhibitory effects on the cytopathogenicity of HIV in MT-4 cells, ddThd and ddeThd completely protected the cells against destruction by the virus at a concentration of 1 microM and 0.04 microM, respectively. In this aspect, ddeThd was about 5 times more potent than 2',3'-dideoxycytidine (ddCyd), one of the most potent and selective anti-HIV compounds now pursued for its therapeutic potential in the treatment of AIDS. ddThd and ddeThd also suppressed HIV antigen expression at 1 microM and 0.04 microM, respectively. Their selectivity indexes, as based on the ratio of the 50% cytotoxic dose to the 50% antiviral effective dose, were 120 (ddeThd) and greater than 625 (ddThd).