Synthesis and preliminary evaluation of anti-HIV agent AZT prodrug.

In this research, phosphate and thiophosphate prodrugs 3a, 3b of anti-HIV agent AZT were synthesized, and their anti-HIV activities and cytotoxicities were investigated in vitro. Results showed that the prodrugs 3a and 3b with an IC50 value of 11.0 and 4.0 micromol x L(-1), respectively, were less toxic than AZT (1.0 micromol x L(-1)). Although the EC50 values of both 3a (0.04 micromol x (L(-1) and 3b (0.16 micromol x L(-1)) were lower than that of AZT (0.01 micromol x L(-1)), the therapeutic index (IC50/EC50) of prodrug 3a (275) was much higher than that of both AZT (100) and prodrug 3b (25). This indicated that the prodrug 3a merited further investigation as an anti-HIV agent.