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

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 vitroanti-TB activity. The whole cell evaluation of minimum inhibitory concentration values of different substituted cinnamic acids and acetamidophenols showed that the free orthohydroxyl group conferred both potency and selectivity. Both 2-coumaric acid and 2-acetamidophenol showed minimum inhibitory concentration below 150 mu M against M. tuberculosisH sub(37)Rv and selectivity index higher than 30.