Synthesis, In-Silico Molecular Docking Studies, and In-Vitro Antimicrobial Evaluation of Isatin Scaffolds bearing 1, 2, 3-Triazoles using Click Chemistry

Bacterial infections continue to present a formidable challenge to human health, prompting intensified research efforts towards the development of effective antibacterial agents. This study harnesses click chemistry techniques to synthesize Isatin-1,2,3-triazole as a novel antibacterial agent, evaluating its in vitro efficacy against prevalent pathogens including Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) strains using both the microdilution and well-diffusion methods. The findings reveal a notable enhancement in antibacterial activity upon incorporation of the triazole moiety into the Isatin framework against both E. coli and S. aureus. Further analysis, including structure–activity relationship studies and molecular docking investigations, highlights the superior antibacterial potency of triazole-tethered Isatin tosyl azide compared to N-propargyl Isatin. Molecular docking simulations with Staphylococcus aureus (PDB ID: 4TU5) and Escherichia coli (PDB ID: 6YD9) proteins exhibit promising binding affinities of − 10.44 kJ/mol and − 8.4 kJ/mol, respectively. Isatin triazole demonstrates favorable gastrointestinal absorption properties, low toxicity profiles, adherence to Lipinski's rule of five, and compliance with Veber and Ghose standards. Furthermore, molecular dynamics simulations attest to the stability of protein complexes over a 100 ns timeframe. Collectively, these findings underscore the therapeutic potential of Isatin triazole compounds against bacterial infections, warranting further clinical exploration to elucidate their mechanisms of action and therapeutic efficacy.