Biological evaluation and structure activity relationship of 9-methyl-1-phenyl- 9H-pyrido[3,4- b]indole derivatives as anti-leishmanial agents

Graphical abstract

Anti-leishmanial activity EC ₅₀ (µM).

L. infantum: promastigotes 1.59 and axenic amastigotes 1.4.

L. donovani: promastigotes 0.9, axenic amastigotes 1.4 and intracellular amstigotes 1.3.

Highlights

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  New anti-leishmanial agents designed through molecular hybridization approach.

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  7d showed potent anti-leishmanial activity against both L. infantum & L. donovani.

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  7d EC ₅₀ against L. infantum promastigotes, axenic amastigotes 1.59 & 1.4 µM.

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  7d EC ₅₀ against L. donovani promastigotes, axenic & intracellular amastigotes 0.91 & 0.91 & 1.4 µM.

Abstract

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 (EC ₅₀ 1.59, 1.47 and 3.73 µM respectively) and amastigotes (EC ₅₀ 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 (EC ₅₀ 0.91, 4.0, 4.57 and 5.02 µM respectively), axenic amastigotes (EC ₅₀ 0.9, 3.5, 2.2 and 3.8 µM respectively) and intracellular amastigotes (EC ₅₀ 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.