Structure-activity relationships and mechanistic studies of novel mitochondria-targeted, leishmanicidal derivatives of the 4-aminostyrylquinoline scaffold
作者:Matteo Staderini、Marta Piquero、María Ángeles Abengózar、Montserrat Nachér-Vázquez、Giulia Romanelli、Pilar López-Alvarado、Luis Rivas、Maria Laura Bolognesi、J. Carlos Menéndez
DOI:10.1016/j.ejmech.2019.03.007
日期:2019.6
A new class of quinoline derivatives, bearing amino chains at C-4 and a styryl group at C-2, were tested on Leishmania donovani promastigotes and axenic and intracellular Leishmania pifanoi amastigotes. The introduction of the C-4 substituent improves the activity, which is due to interference with the mitochondrial activity of the parasite and its concomitant bioenergetic collapse by ATP exhaustion
在Leishmania donovani promastigotes以及轴突和胞内Leishmania pifanoi amastigotes上测试了一类新的喹啉衍生物,它们在C-4处带有氨基链,在C-2上具有一个苯乙烯基。C-4取代基的引入提高了活性,这是由于干扰了该寄生虫的线粒体活性及其伴随的ATP耗尽所引起的生物能崩溃。某些化合物显示出令人满怀希望的抗疟药谱,对前鞭毛体和鞭毛体形式的微摩尔或亚微摩尔活性低,且选择性指数高。