Antimalarial Activity of Pyrroloiminoquinones from the Australian Marine Sponge Zyzzya sp

Autor: William N. Charman, Ronald J. Quinn, Rohan A. Davis, Malcolm Stewart Buchanan, Vicky M. Avery, Susan A. Charman, Sandra Duffy, Karen L. White, Katherine T. Andrews, David Brian Camp, Michael D. Edstein, David M. Shackleford
Rok vydání: 2012
Předmět:
Zdroj: Journal of Medicinal Chemistry. 55:5851-5858
ISSN: 1520-4804
0022-2623
DOI: 10.1021/jm3002795
Popis: A new bispyrroloiminoquinone alkaloid, tsitsikammamine C (1), displayed potent in vitro antimalarial activity with IC(50) values of 13 and 18 nM against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum, respectively. Tsitsikammamine C (1) displayed selectivity indices of200 against HEK293 cells and inhibited both ring and trophozoite stages of the malaria parasite life cycle. Previously reported compounds makaluvamines J (2), G (3), L (4), K (5) and damirones A (6) and B (7) were also isolated from the same marine sponge (Zyzzya sp.). Compounds 2-4 displayed potent growth inhibitory activity (IC(50)100 nM) against both P. falciparum lines and only moderate cytotoxicity against HEK293 cells (IC(50) = 1-4 μM). Makaluvamine G (3) was not toxic to mice and suppressed parasite growth in P. berghei infected mice following subcutaneous administration at 8 mg kg(-1) day(-1).
Databáze: OpenAIRE