Isatin based 1,2,3-triazole derivatives as antimicrobial agents: Synthesis, in silico docking and molecular dynamics simulations

Abstract

With the aim to identify new antimicrobials, in the present study a new series of isatin based 1,2,3-triazoles (5a-5f & 6a-6f) has been synthesized through CuAAC click reaction and characterized by FTIR, NMR and MS spectral methods. In vitro antimicrobial assay suggested that synthesized derivatives exhibited good to high efficacy against tested microorganisms. Compounds 5c, 5d, 5f exhibited promising potency towards E. coli, similarly, 5b, 5d, 5e and 6d displayed good antifungal efficacy against C. albicans. These compounds also exhibited better potency against both the fungal strains as compared to the standard drug. Molecular docking studies of these derivatives performed against antibacterial and antifungal targets 1KZN (E. coli) and 5TZ1(C. albicans) revealed that hybrid 5b possessed lowest binding energy i.e. -9.1 kcal/mol and -11.0 kcal/mol, respectively. Moreover, Molecular Mechanics/Poisson-Boltzmann Surface Area (MM/PBSA) analysis was used to compute the various components contributing to binding free energy of 5b with these biological targets.