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

作者：Davis Rohan A; Buchanan Malcolm S; Duffy Sandra; Avery Vicky M; Charman Susan A; Charman William N; White Karen L; Shackleford David M; Edstein Michael D; Andrews Katherine T; Camp David; Quinn Ronald J^*

来源：Journal of Medicinal Chemistry, 2012, 55(12): 5851-5858.

DOI：10.1021/jm3002795

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 %26gt;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 2-4 displayed potent growth inhibitory activity (IC50 %26lt; 100 nM) against both P. falciparum lines and only moderate c-ytotoxicity against HEK293 cells (IC50 = 1-4 mu 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(-1) day(-1).

• 出版日期2012-6-28