New semisynthetic quassinoids with in vivo antimalarial activity.
On the basis of a comparative analysis for stability in mouse serum between 15-O-acetylbruceolide and bruceolide 15-methyl carbonate, several 3,15-dialkyl carbonates of bruceolide were synthesized and their in vitro antimalarial activity was assessed. Methyl, ethyl, and isopropyl carbonates with pronounced in vitro activity were further evaluated for in vivo antimalarial potency. Both the methyl and ethyl carbonates significantly increased the life span of mice as compared with 3,15-di-O-accetylbruceolide and chloroquine.
Murakami
Nobutoshi
N
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Sugimoto
Masanori
M
Kawanishi
Motoyuki
M
Tamura
Satoru
S
Kim
Hye-Sook
HS
Begum
Khurshida
K
Wataya
Yusuke
Y
Kobayashi
Motomasa
M
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D004355:Drug Stability; D008288:Malaria / Q000188:drug therapy; D051379:Mice; D010962:Plasmodium berghei; D010963:Plasmodium falciparum / Q000187:drug effects*; D036702:Quassins / Q000138:chemical synthesis* / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000962:Antimalarials; D036702:Quassins