Antimalarial agents, 4. Synthesis of a brusatol analog and biological activity of brusatol-related compounds.
The quassinoids bruceoside-A [1], brusatol [2], and bruceolide [3] were tested for antimalarial activity in vitro against the chloroquine-resistant (Smith) isolates of Plasmodium falciparum. Compound 2 was quite active, 1 was not active, and 3 showed only a trace of activity. The fact that 15 [(E)-non-2-enoyl] bruceolide [7] synthesized from 2 was eight times less active than 2 would indicate that the requirement of a C-15 ester moiety for enhanced antimalarial activity among brusatol related quassinoids could be quite specific.
Lee
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Division of Medicinal Chemistry and Natural Products, School of Pharmacy, University of North Carolina, Chapel Hill 27514.
Tani
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S
Imakura
Y
Y
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D005900:Glaucarubin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D010616:Phenanthrenes / Q000138:chemical synthesis*; D010963:Plasmodium falciparum / Q000187:drug effects; D036702:Quassins
D000962:Antimalarials; D010616:Phenanthrenes; D036702:Quassins; C020237:brusatol; D005900:Glaucarubin