Division of Medicinal and Process Chemistry, Central Drug Research Institute , Lucknow , India.
J Enzyme Inhib Med Chem. 2013 Oct;28(5):1048-53. doi: 10.3109/14756366.2012.710848. Epub 2012 Sep 7.
A new series of quinoline analogs have been synthesized and found active against P. falciparum in vitro and P. yoelli in vivo. Compounds 8, 10 and 11 exhibited superior in vitro activity compared to chloroquine. Selected compounds 8, 10 and 11 exhibited significant suppression of parasitaemia in vivo assay. These analogs form a complex with hematin and inhibit the β-hematin formation, suggesting that this class of compounds act on a heme polymerization target. Further this study confirms that quinoline ring nitrogen is essential for both transportation of the molecule across the membrane as well as for tight binding to hematin.
已合成了一系列新的喹啉类似物，并发现其对体外的疟原虫和体内的约氏疟原虫具有活性。化合物 8、10 和 11 的体外活性优于氯喹。选定的化合物 8、10 和 11 对体内寄生虫血症检测显示出显著的抑制作用。这些类似物与血红素形成复合物并抑制β-血红素形成，表明该类化合物作用于血红素聚合靶标。此外，本研究证实喹啉环氮原子对于分子穿过细胞膜的运输以及与血红素的紧密结合都是必需的。
