Rational Design and Synthesis of Novel Diphenyl ether Derivatives as Antitubercular Agents

Kar, Sidhartha S and Bhat, Vadiraja G and Shenoy, Vishnu Prasad and Bairy, Indira and Shenoy, Gautham G (2016) Rational Design and Synthesis of Novel Diphenyl ether Derivatives as Antitubercular Agents. Drug Design, Development and Therapy, 10. pp. 2299-2310. ISSN 1177-8881

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A series of triclosan mimic diphenyl ether derivatives have been synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The binding mode of the compounds at the active site of enoyl-acyl carrier protein reductase of M. tuberculosis has been explored. Among them, compound 10b was found to possess antitubercular activity (minimum inhibitory concentration =12.5 μg/mL) comparable to triclosan. All the synthesized compounds exhibited low levels of cytotoxicity against Vero and HepG2 cell lines, and three compounds 10a, 10b, and 10c had a selectivity index more than 10. Compound 10b was also evaluated for log P, pKa, human liver microsomal stability, and % protein binding, in order to probe its druglikeness. Based on the antitubercular activity and druglikeness profile, it may be concluded that compound 10b could be a lead for future development of antitubercular drugs.

Item Type: Article
Uncontrolled Keywords: Diphenyl ether; Tuberculosis; Cytotoxicity; Druglikeness
Subjects: Medicine > MMMC Manipal > Microbiology
Medicine > KMC Manipal > Microbiology
Pharmacy > MCOPS Manipal > Pharmaceutical Chemistry
Depositing User: KMC Library
Date Deposited: 19 Jan 2017 08:47
Last Modified: 19 Jan 2017 08:47
URI: http://eprints.manipal.edu/id/eprint/148149

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