Synthesis and preliminary evaluation of anti-HIV agent AZT prodrug.
- Author:
Qing-Bin CUI
1
;
Gao-Xiao ZHANG
;
Pei YU
;
Yu-Qiang WANG
Author Information
1. Institute of New Drug Research, College of Pharmacy, Jinan University, Guangzhou 510632, China.
- Publication Type:Journal Article
- MeSH:
Anti-HIV Agents;
chemical synthesis;
chemistry;
pharmacology;
CD4-Positive T-Lymphocytes;
cytology;
Cell Proliferation;
drug effects;
Cells, Cultured;
Humans;
Inhibitory Concentration 50;
Prodrugs;
chemical synthesis;
chemistry;
pharmacology;
Zidovudine;
analogs & derivatives;
chemical synthesis;
chemistry;
pharmacology
- From:
Acta Pharmaceutica Sinica
2011;46(8):1015-1018
- CountryChina
- Language:English
-
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.
