Rational modification of a lead molecule: Improving the antifungal activity of indole – triazole – amino acid conjugates.

Rational modification of a lead molecule: Improving the antifungal activity of indole – triazole – amino acid conjugates.

Eur J Med Chem. 2018 Jun 18;155:658-669

Authors: Mishra S, Kaur M, Chander S, Murugesan S, Nim L, Arora DS, Singh P

Abstract
The modification of a molecule that was identified as highly efficacious in the previous studies could considerably improve the biological activity of the resulting compounds. While targeting lanosterol 14-α demethylase, the molecular modelling studies convinced that the extension of the phenyl ring of compound 1 deep into the hydrophobic pocket of the enzyme may increase the enzyme – ligand interactions and hence improve the anti-fungal profile of the molecules. As a result, the newly designed compounds 2 were synthesized and screened for their anti-microbial properties and these compounds were found to exhibit considerably better activity than the previous molecule 1. Some of the compounds in this series exhibited MIC90 16 μg mL-1 and 32 μg mL-1 against Candida albicans and Aspergillus niger, respectively as against 312 μg mL-1 for compound 1.

PMID: 29936353 [PubMed – as supplied by publisher]

Source: Industry