Département de Pharmacochimie Moléculaire, Université de Grenoble I/CNRS, UMR 5063, 470 rue de la Chimie, BP 53 F-38041, Grenoble Cedex 9, France.
Bioorg Med Chem. 2010 Aug 1;18(15):5724-31. doi: 10.1016/j.bmc.2010.06.008. Epub 2010 Jun 9.
We report the synthesis and in vitro antiplasmodial activity of 35 compounds, designed as analogues of the naturally occurring aurones. Several of these analogues showed submicromolar antimalarial activity against a chloroquine-resistant strain of Plasmodium falciparum (FcB1-Columbia strain) cultured on human erythrocytes. Substitution of the intracyclic oxygen in aurones by a nitrogen atom and systematic variation of the substituent at the B-ring revealed promising leads showing good activity on the CQ-resistant strain. In particular, 4,6-dimethoxy-4'-ethylazaaurone 22 showed antiplasmodial potency without noticeable toxicity. The easy synthesis of this family of compounds and the relevant antiplasmodial activity are in favor of promising candidates for further development.
我们报告了 35 种化合物的合成及其体外抗疟活性，这些化合物被设计为天然存在的奥罗酮的类似物。其中一些类似物对在人红细胞上培养的氯喹抗性疟原虫（FcB1-Columbia 株）表现出亚微摩尔抗疟活性。在奥罗酮中用氮原子取代内环中的氧，并系统地改变 B 环上的取代基，揭示了有希望的先导化合物，对 CQ 抗性株表现出良好的活性。特别是，4,6-二甲氧基-4'-乙基氮杂奥罗酮 22 表现出抗疟效力，而没有明显的毒性。这类化合物的易于合成和相关的抗疟活性有利于进一步开发有前途的候选药物。
