Anti-HIV Activities of Novel Nucleoside Analogues: Acyclic and Tricyclic Base Nucleosides

Abstract

Two series of new nucleoside derivatives, acyclic nucleosides and tricyclic base nucleosides, were screened for cellular toxicity and against HIV-1. Compounds were tested on MT4, MT2, U937 cell lines and PBMCs in multiwell tissue culture plates. Cells were infected in vitro with 2 TCID50/105 cells or 0.2 TCID50/105 cells of HIV-1-LAV-1. Two out of eight tricyclic derivatives showed little cytotoxicity; at 100μM, only two acyclic compounds exhibited cellular toxicity in U937 cells. In vitro, none of these 19 compounds demonstrated any efficient activity against the lentiviral HIV infection and replication. Furthermore, combinations of these acyclonucleosides with ddC or AZT did not inhibit HIV-1-LAV-1 replication additively or synergistically. Because acyclonucleosides did not induce any cytotoxic effect, other compounds of this family should be investigated.