Department of Chemistry, Faculty of Science, Rhodes University, Makhanda 6140, South Africa.
Department of Chemistry, Faculty of Science, Rhodes University, Makhanda 6140, South Africa; Centre of Excellence for Pharmaceutical Sciences, North-West University, Potchefstroom 2520, South Africa.
Bioorg Med Chem Lett. 2021 Apr 15;38:127855. doi: 10.1016/j.bmcl.2021.127855. Epub 2021 Feb 18.
Several classes of antimalarial drugs are currently available, although issues of toxicity and the emergence of drug resistant malaria parasites have reduced their overall therapeutic efficiency. Quinoline based antiplasmodial drugs have unequivocally been long-established and continue to inspire the design of new antimalarial agents. Herein, a series of mono- and bisquinoline methanamine derivatives were synthesised through sequential steps; Vilsmeier-Haack, reductive amination, and nucleophilic substitution, and obtained in low to excellent yields. The resulting compounds were investigated for in vitro antiplasmodial activity against the 3D7 chloroquine-sensitive strain of Plasmodium falciparum, and compounds 40 and 59 emerged as the most promising with IC values of 0.23 and 0.93 µM, respectively. The most promising compounds were also evaluated in silico by molecular docking protocols for binding affinity to the {001} fast-growing face of a hemozoin crystal model.
目前有几类抗疟药物，但毒性问题和抗疟寄生虫的出现降低了它们的整体治疗效果。基于喹啉的抗疟药物已经得到明确证实，并继续激发新的抗疟药物的设计。在此，通过连续的步骤(Vilsmeier-Haack、还原胺化和亲核取代)合成了一系列单和双喹啉甲胺衍生物，并以低至优异的产率获得。对所得化合物进行了体外抗疟活性测定，以评估它们对氯喹敏感的 3D7 恶性疟原虫菌株的活性，化合物 40 和 59 表现出最有前途的活性，IC 值分别为 0.23 和 0.93µM。最有前途的化合物还通过分子对接方案进行了计算机评估，以评估它们与血红蛋白晶体模型{001}快速生长面的结合亲和力。
