MTK5R6E: A Novel Potent inhibitor of MDR and XDR Mycobacterium tuberculosis isolates

This study reports the antimycobacterial potential of (5R,6E)-5-hydroxy-1,7-diphenyl-6-hepten-3-one (MTK5R6E) against drug-sensitive and drug-resistant Mycobacterium tuberculosis. Using MGIT drug susceptibility testing, the compound exhibited a minimum inhibitory concentration (MIC) of 2 µg/mL against H37Rv as well as rifampicin-, levofloxacin-, and bedaquiline-resistant strains, indicating activity against MDR and XDR isolates. No activity was observed against Mycobacterium abscessus. In silico evaluation demonstrated favorable drug-likeness, lead-likeness, and high gastrointestinal absorption. Density functional theory (DFT) analysis revealed a HOMO–LUMO energy gap of ~5 eV and a suitable electrostatic potential distribution, supporting the observed biological activity. These findings highlight MTK5R6E as a promising lead compound for the development of new therapeutics against multidrug-resistant tuberculosis.