ABSTRACT
Objective To design and synthesize Danshensu derivatives to study the role of hydroxyl group n Danshensu's bio-activity. Methods The phenolic and carboxyl groups of Danshensu were protected by benzyl, and then he hydroxyl group underwent reaction with different catalysts o get hydroxyl modified derivatives through ether and ester bonds, then benzyl groups were removed o get target derivatives. These derivatives were evaluated n H9c2 cells against tert-butyl hydroperoxide induced injury o illustrate the structure-activity relationship. Results Eleven derivatives were synthesized, and heir structures were confirmed by MS, NMR and elemental analysis. Biological results showed that neither ether nor ester derivatives showed better anti-oxidative effects than Danshensu. Conclusion The free hydroxyl group may be necessary for Danshensu's activity.
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.