Ugwu David Izuchukwu, Okoro Uchechukwu Chris, Mishra Narendra Kumar
Medicinal Chemistry Unit, Department of Pure and Industrial Chemistry, University of Nigeria, Nsukka, Nigeria.
Department of Chemistry, Indian Institute of Technology, Kanpur, India.
PLoS One. 2018 Jan 11;13(1):e0191234. doi: 10.1371/journal.pone.0191234. eCollection 2018.
The reported toxicities of current antitrypanosomal drugs and the emergence of drug resistant trypanosomes underscore the need for the development of new antitrypanosomal agents. We report herein the synthesis and antitrypanosomal activity of 24 new amide derivatives of 3-aminoquinoline, bearing substituted benzenesulphonamide. Nine of the new derivatives showed comparable antitrypanosomal activities at IC50 range of 1-6 nM (melarsoprol 5 nM). Compound 11n and 11v are more promising antitrypanosomal agents with IC50 1.0 nM than the rest of the reported derivatives. The novel compounds showed satisfactory predicted physico-chemical properties including oral bioavailability, permeability and transport properties.
目前抗锥虫药物已报道的毒性以及耐药锥虫的出现凸显了开发新型抗锥虫药物的必要性。我们在此报告了24种带有取代苯磺酰胺的3-氨基喹啉新酰胺衍生物的合成及其抗锥虫活性。其中九种新衍生物在IC50为1 - 6 nM（美拉胂醇为5 nM）范围内表现出相当的抗锥虫活性。化合物11n和11v是比其他已报道衍生物更有前景的抗锥虫药物，其IC50为1.0 nM。这些新型化合物显示出令人满意的预测物理化学性质，包括口服生物利用度、通透性和转运性质。
