New anti-malarial peroxides with in vivo potency derived from spongean metabolites.
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.
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Nobutoshi
N
Murakami
Motoyuki
M
Kawanishi
Huq Mohammad
HM
Mostaqul
Jie
J
Li
Sawako
S
Itagaki
Toshihiro
T
Horii
Motomasa
M
Kobayashi
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D015195:Drug Design; D051379:Mice; D010545:Peroxides / Q000138:chemical synthesis* / Q000627:therapeutic use*; D011161:Porifera; D013329:Structure-Activity Relationship
D000962:Antimalarials; D010545:Peroxides