University of Zagreb Faculty of Pharmacy and Biochemistry, Department of Medicinal Chemistry, A. Kovačića 1, HR-10 000, Zagreb, Croatia.
University of Zagreb Faculty of Pharmacy and Biochemistry, Department of Medicinal Chemistry, A. Kovačića 1, HR-10 000, Zagreb, Croatia.
Eur J Med Chem. 2019 Nov 15;182:111640. doi: 10.1016/j.ejmech.2019.111640. Epub 2019 Aug 23.
Numerous modifications of the well-known antimalarial drug primaquine, both at the quinoline ring and at the primary amino group, have been reported, mostly to obtain antimalarial agents with improved bioavailability, reduced toxicity and/or prolonged activity. Modifications of the terminal amino group were made with the main idea to prevent the metabolic pathway leading to inactive and toxic carboxyprimaquine (follow-on strategy), but also to get compounds with different activity (repurposing strategy). The modifications undertaken until 2009 were included in a review published in the same year. The present review covers various classes of primaquine N-derivatives with diverse biological profiles, prepared in the last decade by our research group as well as the others. We have summarized the synthetic procedures applied for their preparation and discussed the main biological results. Several hits for the development of novel antiplasmodial, anticancer, antimycobacterial and antibiofilm agents were identified.
已经报道了许多对著名抗疟药物伯氨喹的修饰，包括喹啉环和伯氨基，主要是为了获得生物利用度更高、毒性更低和/或活性延长的抗疟药物。末端氨基的修饰主要是为了防止导致无活性和有毒的羧基伯氨喹的代谢途径（后续策略），但也为了得到具有不同活性的化合物（重新定位策略）。截至 2009 年的修饰被包含在同年发表的一篇综述中。本综述涵盖了过去十年中我们研究小组以及其他小组制备的各种伯氨喹 N-衍生物类，具有不同的生物学特征。我们总结了用于制备它们的合成步骤，并讨论了主要的生物学结果。已经确定了几种新型抗疟、抗癌、抗分枝杆菌和抗生物膜药物的候选物。
