Synthesis and Antimalarial activity of 3,3-spiroanellated 5,6-disubstituted-1,2,4-trioxanes

Abstract

Novel 3,3-spiroanellated 5-aryl, 6-arylvinyl substituted 1,2,4-trioxanes 19-34 have been syn-thesized and appraised for their antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in swiss mice by oral route at the doses ranging from 96 mg/kg x 4 days to 24 mg/kg x 4 days. 1,2,4-trioxane 25 the most active compounds of the series, provided 100% protection at 24 mg/kg x 4 days and other 1,2,4-trioxanes 22, 26, 27 and 30 also showed promising activity. In this model β-arteether provided 100% and 20% protection at 48 mg/kg x 4 days and 24 mg/kg x 4 days, respectively by oral route.