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.
Singh
Chandan
C
Division of Medicinal and Process Chemistry, Central Drug Research Institute, Lucknow 226001, India. chandancdri@yahoo.com
Sharma
Upasana
U
Saxena
Gunjan
G
Puri
Sunil K
SK
D000284:Administration, Oral; D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D018432:Drug Resistance, Multiple; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D051379:Mice; D010967:Plasmodium yoelii / Q000187:drug effects; D013256:Steroids / Q000737:chemistry*
C503429:1,2,4-trioxane; D000962:Antimalarials; D006571:Heterocyclic Compounds; D013256:Steroids