Department of Chemistry, Faculty of Science, Rhodes University, Makhanda, South Africa.
Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom, South Africa.
Arch Pharm (Weinheim). 2021 Jul;354(7):e2000331. doi: 10.1002/ardp.202000331. Epub 2021 Mar 12.
A rationally designed series of 2-(N-cyclicamino)quinolines coupled with methyl (E)-3-(2/3/4-aminophenyl)acrylates was synthesized and subjected to in vitro screening bioassays for potential antiplasmodial and antitrypanosomal activities against a chloroquine-sensitive (3D7) strain of Plasmodium falciparum and nagana Trypanosoma brucei brucei 427, respectively. Substituent effects on activity were evaluated; meta-acrylate 24 and the ortho-acrylate 29 exhibited the highest antiplasmodial (IC = 1.4 µM) and antitrypanosomal (IC = 10.4 µM) activities, respectively. The activity against HeLa cells showed that the synthesized analogs are not cytotoxic at the maximum tested concentration. The ADME (absorption, distribution, metabolism, and excretion) drug-like properties of the synthesized compounds were predicted through the SwissADME software.
设计合理的一系列 2-(N-环氨基)喹啉与甲基(E)-3-(2/3/4-氨基苯基)丙烯酸盐偶联，然后进行体外筛选生物测定，以评估它们对氯喹敏感（3D7）株恶性疟原虫和冈比亚锥虫 Trypanosoma brucei brucei 427 的潜在抗疟原虫和抗锥虫活性。评估了取代基对活性的影响；间丙烯酸盐 24 和邻丙烯酸盐 29 表现出最高的抗疟原虫（IC = 1.4 µM）和抗锥虫（IC = 10.4 µM）活性。对 HeLa 细胞的活性表明，在所测试的最大浓度下，合成的类似物没有细胞毒性。通过 SwissADME 软件预测了合成化合物的 ADME（吸收、分布、代谢和排泄）类药性。
