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

ABSTRACT: A series of piperazinyl-?-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.

SUBMITTER: Ashok P 

PROVIDER: S-EPMC6369240 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature