Design, Synthesis, Biological Evaluation and Molecular Dynamic Simulation Studies of Diphenyl Ether Derivatives as Antitubercular and Antibacterial Agents

Abstract Tuberculosis is one of the leading cause of death worldwide and Mycobacterium tuberculosis still remains to be the fatal human pathogen. In pursuit of novel diphenyl ethers as antitubercular and antibacterial agents, a series of novel substituted N‐(3‐hydroxy‐4‐phenoxybenzyl)‐N‐phenylmethanesulfonamides 4 a‐k were rationally designed, synthesized and evaluated for their in vitro antitubercular and antibacterial activities. Compounds 4 j and 4 d appeared to be the most promising against Mycobacterium tuberculosis strain H37Rv with minimum inhibitory concentration (MIC) of 42 μM and 65 μM, respectively. Compound 4 j exhibited good in vitro antibacterial activity with MIC of 6.97 μM, 13.94 μM, and 27.88 μM against Escherichia coli, Bacillus subtilis, and Pseudomonas aeruginosa respectively, indicating it's broad‐spectrum of activity. The safety profile of the compounds was assessed on HepG2, Vero and RAW 264.7 cell lines. Molecular docking and molecular dynamics simulation studies were performed to study the binding behavior of the compounds.