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

被引:65
作者
Davis, Rohan A. [1 ]
Buchanan, Malcolm S. [1 ]
Duffy, Sandra [1 ]
Avery, Vicky M. [1 ]
Charman, Susan A. [2 ]
Charman, William N. [2 ]
White, Karen L. [2 ]
Shackleford, David M. [2 ]
Edstein, Michael D. [3 ]
Andrews, Katherine T. [1 ]
Camp, David [1 ]
Quinn, Ronald J. [1 ]
机构
[1] Griffith Univ, Eskitis Inst, Brisbane, Qld 4111, Australia
[2] Monash Univ, Ct Drug Candidate Optimisat, Parkville, Vic 3052, Australia
[3] Australian Army Malaria Inst, Brisbane, Qld 4051, Australia
基金
澳大利亚研究理事会;
关键词
PLASMODIUM-FALCIPARUM MALARIA; WATER CARIBBEAN SPONGE; NATURAL-PRODUCTS; PYRROLOQUINOLINE ALKALOIDS; DRUG DISCOVERY; CYTOTOXIC PYRROLOIMINOQUINONES; BIOSYNTHETIC-ENZYMES; THERAPEUTIC TARGETS; GENUS LATRUNCULIA; DISCORHABDIN-C;
D O I
10.1021/jm3002795
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
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 2-4 displayed potent growth inhibitory activity (IC50 < 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).
引用
收藏
页码:5851 / 5858
页数:8
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