Design, Synthesis, and Antibacterial Evaluation of Novel Coumarin Based 1,2,3-Triazole Derivatives

Objective: Coumarin and triazole moiety itself is well known to have wide range of biological properties including antibacterial activities. In this work, we have designed and synthesized a series of novel coumarin based 1,2,3-triazole derivatives (VIa-VIi) and reported them as potent antibacterial agent. Methods: All the synthesized compounds were characterized using different spectroscopic methods. The antibacterial properties of our designed compounds were evaluated by calculating the minimum inhibitory concentration (MIC) against the bacterial panel Escherichia coli (E. coli), Pseudomonas aeruginosa (P. aeruginosa), Staphylococcus aureus (S. aureus), and Bacillus subtilis (B. subtilis). Further, molecular docking analysis were also performed in order to determine the binding modes and binding energies of the potent hybrids. The in silico method has been used for determining the absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of (VIc), (VId), (VIg), and (VIh). Results and Discussion: Here, we have successfully synthesized nine novel coumarin based 1,2,3-triazole conjugates using cycloaddition reaction. All the compounds were found to be active against the tested bacterial panel with MIC values ranging from 12.5 to 200 mu g/mL. Among them four compounds (VIc), (VId), (VIg), and (VIh) showed broad spectrum of antibacterial activities. Out of these four, the compound (VIh) showed excellent inhibitory action against B. subtilis and compounds (VIg), (VIh) showed great inhibition activity against S. aureus in comparison to the standard drug streptomycin. The molecular docking study also revealed the binding capabilities of our designed compounds with the different active site of the protein (PDB ID: 4OZ5) extracted from B. subtilis with great affinity. Conclusions: From the calculated MIC values, we can conclude that our compounds can act as a potent antibacterial agent against the tested bacteria panel. The in silico results also help to understand the mode of inhibitory action and justify the potential of the synthesized compounds as excellent antibacterial agent.