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

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.