Degradation products antimalarial drug-dihydroartemisinin

Abstract

Dihydroartemisinin (DHA), the biologically active metabolite of artemisinin derivative, is more effectively than other antimalarial drugs in its group. Recent report showed that in stress condition such as long time storage or high temperature, DHA could generate degradation products . In this study, chemical structures and biological activity of DHA degradation products were investigated. Chemical structures were analyzed by spectroscopy techniques. DHA has produced two main degradation products , which are 1, (2R, 3R, 6S)-2-(3-oxobutyl)-3-methyl-6- [(R)-2-propanol]-cyclohexane or (2S, 3R, 6R)-2-(3-oxobutyl)-3-methyl-6-[(R)-2- propanol]-cyclohexane and 2, (2S, 3R, 6S)-2-(3-oxobutyl)-3-methyl-6-[(R)-2- propanol]-cyclohexane . From cytotoxicity testing, these degradation products and DHA were test against 8 cell lines; 3T3, IEC-6, Vero, L929, BHK , HepG2 , Caco2 and MCF7, using the MTT assay . The degradation products show no toxicity to all cell lines, whereas DHA is toxic to IEC-6 and Vero. Additionaly, animal studies with Mice ICR strain given oral administration have shown that degradation products are less toxic than DHA itself. For antimalarial activity testing, degradation products showed no strong inhibition compare to DHA.