LAUSR

Tuberculosis, an airborne infectious disease, results in a high morbidity and mortality rate. The continuous emergence of TB resistance strains including MDR (multidrug‐resistant tuberculosis), XDR (extensive drug‐resistant tuberculosis), and especially TDR (totally drug‐resistant tuberculosis) is a major public health threat and has intensified the need to develop new antitubercular agents. A natural product, curcumin, possesses diverse biological activities but suffers due to a lack of water solubility and bioavailability. To overcome these limitations, a series of 17 water‐soluble monocarbonyl curcuminoids was synthesized and evaluated for antimycobacterial activity. All compounds exhibited good to moderate anti‐TB activity with MIC99 in the range of 3.12–25.0 µM, out of which 7c and 7p were found the most potent compounds with MIC99 in the range of 3.12–6.25 µM. Furthermore, these compounds were observed to be nonhaemolytic, nontoxic, and stable under both physiological as well as reducing conditions. In‐vitro metabolic stability data of the representative compound 7p with the human liver microsome revealed that these compounds possess a moderate metabolism with a half‐life of 1.2 h and an intrinsic clearance of 1.12 ml/h/mg.