1,4-萘醌阳离子作为抗疟药：羟基、酰氧基和烷氧基取代类似物
1,4-naphthoquinone cations as antiplasmodial agents: hydroxy-, acyloxy-, and alkoxy-substituted analogues.
作者信息
Lu Xiao, Altharawi Ali, Gut Jiri, Rosenthal Philip J, Long Timothy E
机构信息
Department of Pharmaceutical and Biomedical Sciences, University of Georgia , Athens, Georgia 30602, United States.
Department of Medicine, San Francisco General Hospital, University of California, San Francisco , Box 0811, San Francisco, California 94143, United States.
出版信息
ACS Med Chem Lett. 2012 Oct 1;3(12):1029-33. doi: 10.1021/ml300242v. eCollection 2012 Dec 13.
Abstract
Cations of hydroxy-substituted 1,4-naphthoquinones were synthesized and evaluated as antiplasmodial agents against Plasmodium falciparum. The atovaquone analogues were found to be inactive as antagonists of parasite growth, which was attributed to ionization of the acidic hydroxyl moiety. Upon modification to an alkoxy substituent, the antiplasmodial activity was restored in the sub-100 nM range. Optimal inhibitors were found to possess IC50 values of 17.4-49.5 nM against heteroresistant P. falciparum W2.
摘要
合成了羟基取代的1,4-萘醌阳离子，并将其作为抗疟原虫剂进行了评估，以对抗恶性疟原虫。发现阿托伐醌类似物作为寄生虫生长的拮抗剂无活性，这归因于酸性羟基部分的离子化。将其修饰为烷氧基取代基后，抗疟活性在低于100 nM的范围内得以恢复。发现最佳抑制剂对异抗性恶性疟原虫W2的IC50值为17.4 - 49.5 nM。
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