Synthesis and biological evaluation of new [1,2,4]triazino[5,6-b]indol-3-ylthio-1,3,5-triazines and [1,2,4]triazino[5,6-b]indol-3-ylthio-pyrimidines against Leishmania donovani

A series of [1,2,4]triazino[5,6-b]indol-3-ylthio-1,3,5-triazines and [1,2,4]triazino[5,6-b]indol-3-ylthio-pyrimidines were synthesized and screened for their in vitro antileishmanial activity against Leishmania donovani. Among all, 8 compounds have shown more than 90% inhibition against promastigotes and IC50 in the range of 4.01–57.78 μM against amastigotes. Compound 5, a triazino[5,6-b]indol-3-ylthio-1,3,5-triazine derivative was found to be the most active and least toxic with 20- & 10-fold more selectivity (S.I. = 56.61) as compared to that of standard drugs pentamidine and sodium stibogluconate (SSG), respectively.

Graphical abstractThe triazino[5,6-b]indol-3-ylthio-1,3,5-triazine derivative (5) is the most potent and is 20-fold more selective, while triazino[5,6-b]indol-3-ylthio-pyrimidine derivative (20) is twofold more selective as an antileishmanial agent, in comparison with pentamidine.Figure optionsDownload full-size imageDownload as PowerPoint slide