Konstantinović Jelena, Videnović Milica, Srbljanović Jelena, Djurković-Djaković Olgica, Bogojević Katarina, Sciotti Richard, Šolaja Bogdan
Faculty of Chemistry, University of Belgrade, Studentski trg 16, P.O. Box 51, 11158 Belgrade, Serbia.
Innovation Center of the Faculty of Chemistry, Studentski trg 12-16, 11158 Belgrade, Serbia.
Molecules. 2017 Feb 24;22(3):343. doi: 10.3390/molecules22030343.
Malaria is a severe and life-threatening disease caused by parasites that are spread to humans through bites of infected mosquitoes. Here, we report on the efficacy of aminoquinolines coupled to benzothiophene and thiophene rings in inhibiting parasite growth. Synthesized compounds were evaluated for their antimalarial activity and toxicity, in vitro and in mice. Benzothiophenes presented in this paper showed improved activities against a chloroquine susceptible (CQS) strain, with potencies of IC = 6 nM, and cured 5/5 infected mice when dosed orally at 160 mg/kg/day × 3 days. In the benzothiophene series, the examined antiplasmodials were more active against the CQS strain D6, than against strains chloroquine resistant (CQR) W2 and multidrug-resistant (MDR) TM91C235. For the thiophene series, a very interesting feature was revealed: hypersensitivity to the CQR strains, resistance index (RI) of <1. This is in sharp contrast to chloroquine, indicating that further development of the series would provide us with more potent antimalarials against CQR strains.
疟疾是一种由寄生虫引起的严重且危及生命的疾病，这些寄生虫通过受感染蚊子的叮咬传播给人类。在此，我们报告了与苯并噻吩和噻吩环偶联的氨基喹啉在抑制寄生虫生长方面的功效。对合成化合物进行了体外和在小鼠体内的抗疟活性及毒性评估。本文所呈现的苯并噻吩对氯喹敏感（CQS）菌株表现出增强的活性，IC50值为6 nM，当以160 mg/kg/天的剂量口服给药3天时，治愈了5/5只受感染小鼠。在苯并噻吩系列中，所检测的抗疟药对CQS菌株D6的活性比对氯喹耐药（CQR）菌株W2和多药耐药（MDR）菌株TM91C235的活性更高。对于噻吩系列，揭示了一个非常有趣的特征：对CQR菌株超敏感，耐药指数（RI）<1。这与氯喹形成鲜明对比，表明该系列的进一步开发将为我们提供更有效的抗CQR菌株的抗疟药。
