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United States Department of Agriculture

Agricultural Research Service

Research Project: DISCOVERY AND DEVELOPMENT OF NATURAL PRODUCT-BASED WEED MANAGEMENT METHODS Title: Synthesis and antitubercular activity of heterocycle substituted diphenyl ether derivatives

Authors
item Kini, Suvarna -
item Bhat, Anilchandra -
item Pan, Zhiqiang
item Dayan, Franck

Submitted to: Journal of Enzyme Inhibition and Medicinal Chemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: January 5, 2010
Publication Date: September 9, 2010
Citation: Kini, S.G., Bhat, A.R., Pan, Z., Dayan, F.E. 2010. Synthesis and antitubercular activity of heterocycle substituted diphenyl ether derivatives. Journal of Enzyme Inhibition and Medicinal Chemistry. 25(5):730-736.

Interpretive Summary: A novel series of heterocyclic substituted diphenyl ether derivatives were synthesized and tested against Mycobacterium Tuberculosis (TB). All ten compounds inhibited the growth of TB at concentrations of 1 ug/mL. This activity was found comparable to the reference drugs rifampicin and isoniazid at the same concentration. The diphenyl ether derivatives did not affect the activity of enoyl reductase, despite their structural similarity with triclosan. Therefore, these compounds appear to have a novel mechanism of action against TB.

Technical Abstract: Despite being an ancient disease, tuberculosis (TB) remains the leading single-agent infectious disease killer in the world. The emerging serious problem due to TB control and clinical management prompted us to synthesize novel series of heterocyclic substituted diphenyl ether derivatives and determine their activity against H37Rv strain of Mycobacterium. All ten compounds inhibited the growth of the H37Rv strain of mycobacterium at concentrations of 1 ug/mL. This activity was found comparable to the reference drugs rifampicin and isoniazid at the same concentration. While the antimicrobial activity of other diphenyl ether analogue, such as triclosan, is associated with the inhibition of ENR, the synthesized substituted diphenyl ether derivatives did not affect this enzyme activity in spite of structural similarity with triclosan. Therefore, these compounds appear to have a novel mechanism of action against M. tuberculosis, and their structural features should be studied further for their potential use as new antitubercular drugs.

Last Modified: 10/20/2014
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