Biological evaluation and structure activity relationship of 9-methyl-1-phenyl-9H-pyrido[3,4-b]indole derivatives as anti-leishmanial agents
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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.
Ashok , P , Chander , S , Smith , T K , Prakash Singh , R , Nath Jha , P & Sankaranarayanan , M 2019 , ' Biological evaluation and structure activity relationship of 9-methyl-1-phenyl- 9H -pyrido[3,4-b]indole derivatives as anti-leishmanial agents ' Bioorganic Chemistry , vol. 84 , pp. 98-105 . https://doi.org/10.1016/j.bioorg.2018.11.037
Copyright © 2018 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).
DescriptionOne of the authors, Ashok Penta, acknowledges Council of Scientific and Industrial Research, New Delhi, India for financial support in the form of Senior Research Fellowship. This work was also partially supported by TKS’s Welcome Trust project grant 093228 and the European Community’s Seventh Framework Program under grant agreement No.602773 (Project KINDRED).
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