Eskitis Institute, Griffith University, Brisbane, QLD 4111, Australia.
J Med Chem. 2012 Jun 28;55(12):5851-8. doi: 10.1021/jm3002795. Epub 2012 Jun 20.
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 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 (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).
一种新的双吡咯并[1,2-a:2',1'-c][1,4]二氮杂喹啉生物碱，即西索卡玛宁 C（1），对氯喹敏感（3D7）和氯喹抗性（Dd2）疟原虫表现出强大的体外抗疟活性，其半数抑制浓度（IC50）分别为 13 和 18 nM。西索卡玛宁 C（1）对 HEK293 细胞的选择性指数>200，并抑制疟原虫生命周期的环和滋养体阶段。先前报道的化合物 makaluvamines J（2）、G（3）、L（4）、K（5）和 damirones A（6）和 B（7）也从同一海绵（Zyzzya sp.）中分离得到。化合物 2-4 对两种疟原虫株均表现出强大的生长抑制活性（IC50<100 nM），对 HEK293 细胞仅有中度细胞毒性（IC50=1-4 μM）。makaluvamine G（3）对小鼠无毒，并在皮下给予 8 mg kg-1 day-1 后抑制疟原虫在感染 P. berghei 的小鼠中的生长。
