Antimalarial Activity of Pyrroloiminoquinones from the Australian Marine Sponge Zyzzya sp.

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• 作者：Rohan A. Davis ; Malcolm S. Buchanan ; Sandra Duffy ; Vicky M. Avery ; Susan A. Charman ; William N. Charman ; Karen L. White ; David M. Shackleford ; Michael D. Edstein ; Katherine T. Andrews ; David Camp ; Ronald J. Quinn
• 刊名：Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：June 28, 2012
• 年：2012
• 卷：55
• 期：12
• 页码：5851-5858
• 全文大小：292K
• 年卷期：v.55,no.12(June 28, 2012)
• ISSN：1520-4804

文摘

A new bispyrroloiminoquinone alkaloid, tsitsikammamine C (1), displayed potent in vitro antimalarial activity with IC₅₀ values of 13 and 18 nM against chloroquine-sensitive (3D7) and chloroquine-resistant (Dd2) Plasmodium falciparum, respectively. Tsitsikammamine C (1) displayed selectivity indices of >200 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鈥?b>4 displayed potent growth inhibitory activity (IC₅₀ < 100 nM) against both P. falciparum lines and only moderate cytotoxicity against HEK293 cells (IC₅₀ = 1鈥? 渭M). Makaluvamine G (3) was not toxic to mice and suppressed parasite growth in P. berghei infected mice following subcutaneous administration at 8 mg kg^鈥? day^鈥?.