Lödige Melanie, Hiersch Luisa
Institute of Organic Chemistry, University of Würzburg, Am Hubland, 97074 Würzburg, Germany.
Int J Med Chem. 2015;2015:458319. doi: 10.1155/2015/458319. Epub 2015 Feb 5.
The effective treatment of malaria can be very complex: Plasmodium parasites develop in multiple stages within a complex life cycle between mosquitoes as vectors and vertebrates as hosts. For the full and effective elimination of parasites, an effective drug should be active against the earliest stages of the Plasmodium infection: liver stages (reduce the progress of the infection), blood stages (cure the clinical symptoms), and gametocytes (inhibit the transmission cycle). Towards this goal, here we report the design, the synthetic methodology, and the characterization of novel hybrid agents with combined activity against Plasmodium liver stages and blood stages and gametocytes. The divergent synthetic approach allows the access to differently linked primaquine-chloroquine hybrid templates in up to eight steps.
疟原虫在作为媒介的蚊子和作为宿主的脊椎动物之间的复杂生命周期内经历多个发育阶段。为了完全有效地消除寄生虫，一种有效的药物应该对疟原虫感染的最早阶段具有活性：肝期（减少感染进程）、血期（治愈临床症状）和配子体（抑制传播周期）。为了实现这一目标，我们在此报告新型杂合剂的设计、合成方法及其特性，这些杂合剂对疟原虫肝期、血期和配子体具有联合活性。这种不同的合成方法允许通过最多八个步骤获得不同连接的伯氨喹 - 氯喹杂合模板。
