Abstract: Malaria remains a global public health problem due to the uphill fight against the causative Plasmodium parasites that are relentless in developing resistance. Indole-based antiplasmodial compounds are endowed with multiple modes of action, of which inhibition of hemozoin formation is the major mechanism of action reported for compounds such as cryptolepine, flinderoles, and isosungucine. Indole-based compounds exert their potent activity against chloroquine-resistant Plasmodium strains by inhibiting hemozoin formation in a mode of action different from that of chloroquine or through a novel mechanism of action. For example, dysregulating the sodium and osmotic homeostasis of Plasmodium through inhibition of PfATP4 is the novel mechanism of cipargamin. The potential of developing multi-targeted compounds through molecular hybridization ensures the existence of indole-based compounds in the antimalarial pipeline.

Keywords: indole, antimalarial agents, hemozoin inhibition, PfATP4, multi-target approach


中文翻译：

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吲哚：抗疟原虫剂的下一个支架？

摘要：疟疾仍然是一个全球性的公共卫生问题，因为与致病的疟原虫进行了艰苦的斗争，这些寄生虫在产生抗药性方面是无情的。基于吲哚的抗疟原虫化合物具有多种作用模式，其中抑制血红素形成是报道的化合物如隐甘平、氟林德罗和异甘氨酸的主要作用机制。基于吲哚的化合物通过以与氯喹不同的作用方式或通过新的作用机制抑制血红素形成，从而对耐氯喹的疟原虫菌株发挥强大的活性。例如，调节疟原虫的钠和渗透稳态通过抑制 PfATP4 是 cipargamin 的新机制。通过分子杂交开发多靶点化合物的潜力确保了抗疟管道中吲哚类化合物的存在。

关键词：吲哚，抗疟药，血红素抑制，PfATP4，多靶点方法