2-Hydroxy-substituted cinnamic acids and acetanilides are selective growth inhibitors of Mycobacterium tuberculosis

Juan D. Guzman; Parisa N. Mortazavi; Tulika Munshi; Dimitrios Evangelopoulos; Timothy D. McHugh; Simon Gibbons; John Malkinson; Sanjib Bhakta

doi:10.1039/c3md00251a

2-Hydroxy-substituted cinnamic acids and acetanilides are selective growth inhibitors of Mycobacterium tuberculosis

Juan D. Guzman, Parisa N. Mortazavi, Tulika Munshi, Dimitrios Evangelopoulos, Timothy D. McHugh, Simon Gibbons, John Malkinson, Sanjib Bhakta

Research output: Contribution to journal › Article › peer-review

45 Citations (Scopus)

Abstract

Selective chemical hits are required for feeding the initial discovery phase of the anti-tuberculosis therapeutics pipeline. These chemical entities should ideally target novel mechanisms of action in order to tackle drug resistance in Mycobacterium tuberculosis. In this work, hydroxycinnamic acid and acetamidophenol skeleta were employed for assessing the effects of constitutional isomerism on in vitro anti-TB activity. The whole cell evaluation of minimum inhibitory concentration values of different substituted cinnamic acids and acetamidophenols showed that the free ortho hydroxyl group conferred both potency and selectivity. Both 2-coumaric acid and 2-acetamidophenol showed minimum inhibitory concentration below 150 μM against M. tuberculosis H 37Rv and selectivity index higher than 30.

Original language	English
Pages (from-to)	47-50
Number of pages	4
Journal	MedChemComm
Volume	5
Issue number	1
Early online date	11 Nov 2013
DOIs	https://doi.org/10.1039/c3md00251a
Publication status	Published - 2014

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10.1039/c3md00251a

Cite this

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abstract = "Selective chemical hits are required for feeding the initial discovery phase of the anti-tuberculosis therapeutics pipeline. These chemical entities should ideally target novel mechanisms of action in order to tackle drug resistance in Mycobacterium tuberculosis. In this work, hydroxycinnamic acid and acetamidophenol skeleta were employed for assessing the effects of constitutional isomerism on in vitro anti-TB activity. The whole cell evaluation of minimum inhibitory concentration values of different substituted cinnamic acids and acetamidophenols showed that the free ortho hydroxyl group conferred both potency and selectivity. Both 2-coumaric acid and 2-acetamidophenol showed minimum inhibitory concentration below 150 μM against M. tuberculosis H 37Rv and selectivity index higher than 30. ",

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AU - Guzman, Juan D.

AU - Mortazavi, Parisa N.

AU - Munshi, Tulika

AU - Evangelopoulos, Dimitrios

AU - McHugh, Timothy D.

AU - Gibbons, Simon

AU - Malkinson, John

AU - Bhakta, Sanjib

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AB - Selective chemical hits are required for feeding the initial discovery phase of the anti-tuberculosis therapeutics pipeline. These chemical entities should ideally target novel mechanisms of action in order to tackle drug resistance in Mycobacterium tuberculosis. In this work, hydroxycinnamic acid and acetamidophenol skeleta were employed for assessing the effects of constitutional isomerism on in vitro anti-TB activity. The whole cell evaluation of minimum inhibitory concentration values of different substituted cinnamic acids and acetamidophenols showed that the free ortho hydroxyl group conferred both potency and selectivity. Both 2-coumaric acid and 2-acetamidophenol showed minimum inhibitory concentration below 150 μM against M. tuberculosis H 37Rv and selectivity index higher than 30.

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