Floxacrine analog WR 243251 inhibits hematin polymerization
Floxacrine analog WR 243251 inhibits hematin polymerization
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DOI：
10.4269/ajtmh.2001.65.19
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发表时间：
2001-07-01
影响因子：
3.3
通讯作者：
Vennerstrom, JL
中科院分区：
文献类型：
--
作者：
Dorn, A;Scovill, JP;Vennerstrom, JL
氟沙克林是一种很有前景的抗疟化合物，最终鉴定出WR 243251。根据它们的结构，我们推测这些化合物可能是很好的血红素聚合抑制剂。事实上，作为这一过程的抑制剂，WR 243251的效力与氯喹一样强，而氟沙克林的效力仅比氯喹低2倍。然而。这种血红素聚合抑制并不能完全解释WR 243251与氯喹相比抗疟效力增加的原因。酮类水解产物WR 243251对血素聚合无抑制作用。这些数据也证实了抑制血素聚合可以对抑制剂结构的微小变化相当敏感。
Floxacrine was a promising antimalarial compound that led to the identification of WR 243251. On the basis of their structures, we suspected that these compounds might be good inhibitors of hematin polymerization. Indeed, WR 243251 was as potent and floxacrine was only 2-fold less potent than chloroquine as inhibitors of this process. However. this hematin polymerization inhibition did not completely account for the increased antimalarial potency of WR 243251 versus chloroquine. The WR 243251 ketone hydrolysis product WR 243246 was without activity against hematin polymerization. These data also confirm that hematin polymerization inhibition can be quite sensitive to small changes in inhibitor structure.