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

• Published in: European journal of medicinal chemistry 2010-06, Vol.45 (6), p.2359-2365
• Main Authors: Gupta, Leena, Sunduru, Naresh, Verma, Aditya, Srivastava, Saumya, Gupta, Suman, Goyal, Neena, Chauhan, Prem M.S.
• Format: Article
• Language: English
• Subjects: 1,3,5-Triazine; Animals; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiparasitic agents; Antiprotozoal Agents - chemical synthesis; Antiprotozoal Agents - chemistry; Antiprotozoal Agents - pharmacology; Antiprotozoal Agents - toxicity; Biological and medical sciences; Cell Line; Cell Survival - drug effects; Drug Evaluation, Preclinical; Inhibitory Concentration 50; Leishmania donovani - drug effects; Leishmania donovani - growth & development; Leishmaniasis; Life Cycle Stages; Medical sciences; Mice; Pharmacology. Drug treatments; Pyrimidine; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; Pyrimidines - toxicity; Triazines - chemical synthesis; Triazines - chemistry; Triazines - pharmacology; Triazines - toxicity; Triazino[5,6- b]indole
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2010.02.015

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 IC 50 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. [Display omitted] The 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.