Synthesis, antimycobacterial evaluation and pharmacophore modeling of analogues of the natural product formononetin

Peggoty Mutai; Elumalai Pavadai; Ian Wiid; Andile Ngwane; Bienyameen Baker; Kelly Chibale

doi:10.1016/j.bmcl.2015.04.064

Synthesis, antimycobacterial evaluation and pharmacophore modeling of analogues of the natural product formononetin

Bioorg Med Chem Lett. 2015 Jun 15;25(12):2510-3. doi: 10.1016/j.bmcl.2015.04.064. Epub 2015 Apr 28.

Authors

Peggoty Mutai¹, Elumalai Pavadai¹, Ian Wiid², Andile Ngwane², Bienyameen Baker², Kelly Chibale³

Affiliations

¹ Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa.
² DST-NRF Centre of Excellence for Biomedical Tuberculosis Research, SAMRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, PO Box 19063, Tygerberg 7505, South Africa.
³ Department of Chemistry, University of Cape Town, Rondebosch 7701, South Africa; South African Medical Research Council, Drug Discovery and Development Research Unit, University of Cape Town, Rondebosch 7701, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Rondebosch 7701, South Africa. Electronic address: [email protected].

PMID: 25977095
DOI: 10.1016/j.bmcl.2015.04.064

Abstract

The synthesis and antimycobacterial activity of formononetin analogues is hereby reported. Formononetin and its analogue 11E showed 88% and 95% growth inhibition, respectively, against the H37Rv strain of Mycobacterium tuberculosis. Pharmacophore modeling studies indicated that the presence of a hydroxyl group in formononetin and its analogues, is crucial for maintaining activity.

Keywords: Activity; Antimycobacterial; Formononetin; Pharmacophore; Structure.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antitubercular Agents / chemical synthesis*
Antitubercular Agents / chemistry
Antitubercular Agents / pharmacology
Biological Products / chemical synthesis*
Biological Products / chemistry
Biological Products / pharmacology
Drug Design
Isoflavones / chemical synthesis*
Isoflavones / chemistry*
Isoflavones / pharmacology
Microbial Sensitivity Tests
Mycobacterium tuberculosis / drug effects
Structure-Activity Relationship

Substances

3-(4-tert-butylphenyl)-7-hydroxy-4H-chromen-4-one
Antitubercular Agents
Biological Products
Isoflavones
formononetin