Evaluation of Antituberculosis Activity and in Silico Properties of Oxymethylene‐cyclo‐1,3‐diones

Abstract

AbstractTuberculosis is a leading infectious disease that has infected one‐third of the world's population and is more prevalent among people belonging to developing countries such as India and China. In the present study, a series of substituted oxymethylene‐cyclo‐1,3‐diones was synthesized and screened for anti‐tuberculosis activity against Mycobacterium tuberculosis H37Rv (M. tuberculosis). The compounds were synthesized by condensation of 1,3‐cyclicdione, substituted phenols/ alcohols and triethyl orthoformate. The synthesized compounds were screened for anti‐tuberculosis activity against M.tuberculosis H37Rv using Middlebrook 7H9 broth assay. Results demonstrated that among the synthesized library of molecules, two compounds 2‐(2‐hydroxyphenoxymethylene)‐5,5‐dimethylcyclohexane‐1,3‐dione and 5,5‐dimethyl‐2‐(2‐trifluoromethylphenoxymethylene)cyclohexane‐1,3‐dione were found to be most active against M. tuberculosis (MICs of 1.25 μg/mL−1). The MICs of 2‐(2,4‐difluoro‐phenoxymethylene)‐5,5‐dimethylcyclohexane‐1,3‐dione and 2‐(2‐bromophenoxymethylene)‐5,5‐dimethylcyclohexane‐1,3‐dione were found to be 5 and 10 μg mL−1, respectively. Data from the 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assay showed that all the four most active compounds did not exhibit cytotoxicity against human cell lines. Molecular docking studies revealed that the most active compound targets mycobacterial InhA enzyme. In summary, the present study demonstrates the methodology for the synthesis of oxymethylene‐cyclo‐1,3‐diones and identified two potential anti‐tuberculosis compounds.