Monocarbonyl curcuminoids as antituberculosis agents with their moderate in-vitro metabolic stability on human liver microsomes

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 mu M, out of which 7c and 7p were found the most potent compounds with MIC99 in the range of 3.12-6.25 mu M. 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.

Automated summary

A series of 17 water-soluble monocarbonyl curcuminoids were synthesized and evaluated for antimycobacterial activity, showing good anti-TB activity. Compounds 7c and 7p were found to be the most potent, which may have potential application in the treatment of tuberculosis.