3-Benzylidene-4-chromanones: a novel cluster of anti-tubercular agents

Abstract

In a quest for developing novel anti-tubercular agents, a series of 3-benzylidene-4-chromanones 1a–l were evaluated for growth inhibition of Mycobacterium tuberculosis H₃₇Rv. Three promising compounds 1d, g, j emerged as the lead compounds with the IC₅₀ and IC₉₀ values of less than 1 µg/mL. Evaluation of the potent compounds 1d, g, j and k against Vero monkey kidney cells revealed that these compounds are far more toxic to M. tuberculosis than to Vero cells. Structure–activity relationships demonstrated that 3-benzylidene-4-chromanones are more potent against M. tuberculosis than the related 2-benzylidene cycloalkanones and the meta substituted chromanone derivatives are more active than their ortho- and para-counterparts. Some guidelines for amplifying the project are presented.

• 4-chromanones
• anti-mycobacterial
• anti-tubercular
• structure–activity relationships
• tuberculosis
• unsaturated ketones

Acknowledgements

The authors thank the Canadian Institutes of Health Research for an operating grant to J. R. Dimmock and the Faculty of Medicine Research Fund PTE AOK-KA-2013/20 (University of Pécs) to P. Perjesi. The anti-tubercular results were provided by the Tuberculosis Antimicrobial Acquisition and Coordinating Facility (TAACF) through a research and development contract with the U.S. National Institute of Allergy and Infectious Diseases. Assistance with the literature surveys was given by Vicky Duncan which is recorded with appreciation.

Declaration of interest

The authors report no conflict of interest and are responsible for the contents and writing of the paper.