Design, Synthesis, Biological Evaluation and Molecular Dynamic Simulation Studies of Diphenyl Ether Derivatives as Antitubercular and Antibacterial Agents. Issue 1 (2nd January 2020)

• Record Type: Journal Article
• Authors: Khade, Amol B.; Eshwara, Vandana K.; Boshoff, Helena I.M.; Arora, Kriti; Tiwari, Ashutosh; Bhat, Pritesh; Tiwari, Mradul; Shenoy, G. Gautham
• Is Part Of: ChemistrySelect. Volume 5:Issue 1(2020)
• Page Start: 201
• Page End: 210
• Publication Date: 2020-01-02
• Subjects: Antitubercular agents -- Diphenyl ethers -- Drug-likeness -- Molecular dynamics simulation -- Triclosan.; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.201903305
• Languages: English
• ISSNs: 2365-6549

Abstract

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. Abstract : Triclosan mimicking novel diphenyl ether derivatives were synthesized and assessed for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. In addition, the compounds were also screened for their in vitro antibacterial activity against two Gram‐positive and two Gram‐negative bacteria. Molecular docking and Molecular dynamics simulation study were also performed to probe the difference in the observed antitubercular activity of compound 4 j in comparison to that of triclosan.