New anti-malarial peroxides with In vivo potency derived from spongean metabolites

N Murakami, M Kawanishi, HM Mostaqul, J Li…

Index: Murakami, Nobutoshi; Kawanishi, Motoyuki; Mostaqul, Huq Mohammad; Li, Jie; Itagaki, Sawako; Horii, Toshihiro; Kobayashi, Motomasa Bioorganic and Medicinal Chemistry Letters, 2003 , vol. 13, # 22 p. 4081 - 4084

Full Text: HTML

Citation Number: 16

Abstract

The structure–activity relationship of the anti-malarial substance 3 having a 6- carbomethoxymethyl-3-methoxy-1, 2-dioxane structure was studied. The ester portion of the peroxide 3, showing little in vivo efficacy in malaria-infected mice in spite of the potent in vitro activity, was hydrolyzed in serum to afford an inactive free acid 4. The amide analogues (8 and 9) robust to mouse serum were disclosed to exhibit in vivo anti-malarial potency.