Issue 63, 2020, Issue in Progress

Synthesis, study of antileishmanial and antitrypanosomal activity of imidazo pyridine fused triazole analogues

Abstract

Four groups, thirty-five compounds in total, of novel 1,2,3-triazole analogues of imidazo-[1,2-a]-pyridine-3-carboxamides were designed and synthesized using substituted pyridine, propargyl bromide, 2-azidoethyl 4-methyl benzenesulfonate and substituted acetylenes. These compounds were characterized using 1H NMR, 13C NMR, LCMS and elemental analyses and a crystal structure was obtained for one of the significantly active compounds, 8f. All the synthesized and characterized compounds were screened in vitro for antileishmanial and antitrypanosomal activity against Leishmania major and Trypanosoma brucei parasites, respectively. Among the tested analogues, five compounds (8d, 8f, 8j, 10b and 10d) exhibited significant antileishmanial activity while three compounds (10b, 11a and 11b) showed substantial activity against T. brucei parasite. In silico ADME prediction studies depicted that the essential compounds obeyed Lipinski's rule of five. The predicted in silico toxicity profile suggested that the tested compounds would be non-toxic, which was confirmed experimentally by the lack of cytotoxicity against HeLa cells. Finally, a molecular docking study was also performed, for 10d the most active antileishmanial compound, to study its putative binding pattern at the active site of the selected leishmanial trypanothione reductase target.

Graphical abstract: Synthesis, study of antileishmanial and antitrypanosomal activity of imidazo pyridine fused triazole analogues

Supplementary files

Article information

Article type
Paper
Submitted
15 Sep 2020
Accepted
13 Oct 2020
First published
19 Oct 2020
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2020,10, 38328-38343

Synthesis, study of antileishmanial and antitrypanosomal activity of imidazo pyridine fused triazole analogues

A. Nandikolla, S. Srinivasarao, B. Karan Kumar, S. Murugesan, H. Aggarwal, L. L. Major, T. K. Smith and K. V. G. Chandra Sekhar, RSC Adv., 2020, 10, 38328 DOI: 10.1039/D0RA07881F

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements