title: Synthesis and preliminary evaluation of anti-HIV agent AZT prodrug.
abstract: 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.
authors: Institute of New Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
authors: Qing-Bin
authors: QB
authors: Cui
authors: Gao-Xiao
authors: GX
authors: Zhang
authors: Pei
authors: P
authors: Yu
authors: Yu-Qiang
authors: YQ
authors: Wang
mesh_terms: D019380:Anti-HIV Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D006801:Humans; D020128:Inhibitory Concentration 50; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: C578918:3'-azido-3'-deoxythymidine-5'-bis(3,3-diacetoxy-propyl)phosphate; D019380:Anti-HIV Agents; D011355:Prodrugs; D015215:Zidovudine