A series of piperazinyl-β-carboline-3-carboxamide derivatives were designed through a molecular hybridization approach. Designed analogues were synthesized, characterized and evaluated for anti-leishmanial activity against Leishmania infantum and Leishmania donovani. In L. infantum inhibition assay, compounds 7d, 7g and 7c displayed potent inhibition of promastigotes (EC50 1.59, 1.47 and 3.73 µM respectively) and amastigotes (EC50 1.4, 1.9 and 2.6 µM respectively). SAR studies revealed that, para substitution of methoxy, chloro groups and methyl group on ortho position favored anti-leishmanial activity against L. infantum. Among these analogues 7d, 7h, 7n and 7g exhibited potent inhibition against L. donovani promastigotes (EC50 0.91, 4.0, 4.57 and 5.02 µM respectively), axenic amastigotes (EC50 0.9, 3.5, 2.2 and 3.8 µM respectively) and intracellular amastigotes (EC50 1.3, 7.8, 5.6 and 6.3 µM respectively). SAR studies suggested that, para substitution of methoxy group, para and meta substitution of chloro groups and benzyl replacement recommended for significant anti-leishmanial against L. donovani.

中文翻译：

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9-甲基-1-苯基-9H-吡啶并[3,4-b]吲哚衍生物作为抗利什曼制剂的生物学评价和结构活性关系。

通过分子杂交方法设计了一系列哌嗪基-β-咔啉-3-羧酰胺衍生物。合成，表征了设计的类似物，并评估了其对婴儿利什曼原虫和多形利什曼原虫的抗利什曼原虫活性。在婴儿乳杆菌的抑制测定中，化合物7d，7g和7c对前鞭毛体（分别为EC50 1.59、1.47和3.73 µM）和变形虫（EC50分别为1.4、1.9和2.6 µM）显示出有效的抑制作用。SAR研究表明，邻位甲氧基，氯基和甲基的对位取代有利于抗婴儿利什曼原虫的活性。在这些类似物7d，7h，7n和7g中，它们显示出对多诺氏乳杆菌前鞭毛体（分别为EC50 0.91、4.0、4.57和5.02μM），轴突性吻合动物（EC50为0.9、3.5、2.2和3）的有效抑制作用。分别为8 µM）和胞内变形虫（EC50分别为1.3、7.8、5.6和6.3 µM）。SAR研究表明，甲氧基的对位取代，氯基的对位和间位取代以及苄基取代被推荐用于对多诺氏乳杆菌有显着的抗利什曼肽作用。