Synthesis and antitubercular activity of heterocycle substituted diphenyl ether derivatives

Abstract

Despite being an ancient disease, tuberculosis (TB) remains the leading single-agent infectious disease killer in the world. The emerging serious problem of TB control and clinical management prompted us to synthesize a novel series of heterocyclic substituted diphenyl ether derivatives and determine their activity against the H37Rv strain of Mycobacterium. All ten compounds inhibited the growth of the H37Rv strain of Mycobacterium at concentrations of 1 μg/mL. This activity was found to be comparable to the reference drugs rifampicin and isoniazid at the same concentration. While the antimicrobial activity of other diphenyl ether analogues, such as triclosan, is associated with the inhibition of enoyl-ACP reductase (ENR), the synthesised substituted diphenyl ether derivatives did not affect this enzyme activity in spite of their 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 as new antitubercular drugs.

Keywords::

• Tuberculosis
• enoyl-ACP reductase
• antitubercular activity

Acknowledgements

We would like to thank the Microbiology Department of Kasturba Medical College, Manipal for helping with the antitubercular assay, and to the Central Drug Research Institute, Lucknow; Indian Institute Science, Bangalore and Indian Institute Chemical Technology, Hyderabad for providing the elemental analysis, ¹H-NMR and Mass spectra of the compounds. ENR assay was performed at USDA-ARS Natural Products Utilization Research Unit, University, MS, USA.

Declaration of Interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.