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

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 MIC 90 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 .