Orally active antimalarials: synthesis and bioevaluation of a new series of steroid-based 1,2,4-trioxanes against multi-drug resistant malaria in mice

A new series of steroid-based 1,2,4-trioxanes 7a-f, 8a-f and 9b-e have been synthesized and evaluated for their antimalarial activity against multi-drug resistant Plasmodium yoelii in Swiss mice by oral route. The biological activity shows a strong dependence on the size and the nature of the steroidal side chain. Pregnane-based trioxanes 8a-f show better activity profile than trioxanes 7a-f and 9b-e, derived from cholesterol and tigogenine, respectively.