Enhanced In Vitro Inhibition of HIV-1 Replication by 3′-Fluoro-3′-deoxythymidine Compared to Several Other Nucleoside Analogs

Nucleoside analogs were synthesized and tested for anti-HIV-1 activity in two in vitro test systems using MT-4 cells and peripheral blood lymphocytes. Cytotoxicity was assessed in both assays and additionally in several human lymphoblastoid cell lines. One analog, 3′fluoro-3′-deoxythymidine, exhibited higher antiviral potency and slightly higher cytotoxicity than 3′-azido-3′-deoxythymidine. Analogs showing lower cytotoxicity than 3′-azido-3′deoxythymidine demonstrated reduced antiviral activity. 3′-Fluoro-3′-deoxythymidine may become an alternative chemotherapeutic agent because of its high antiretro viral potency. Its toxicity, however, deserves further investigation.