Anti-Bacterial Activity of Furan Chalcone Derivatives Against Mycobacterium tuberculosis: Design, Synthesis,...

A novel series of fifty furan-based chalcone derivatives and their potential anti-bacterial activity against Mycobacterium tuberculosis was studied in this present work. The pharmacokinetic properties and toxicity parameters of these designed molecules were studied using in silico methods. Physicochemical parameters were computed for all the designed molecules and Swiss ADME analysis demonstrated that the designed compounds possess good drug-like properties. Among them top 10 compounds were selected based on initial ADME screening and subjected to docking investigations using the Autodock Tool. 1.5.6. The binding energies and interactions of these compounds with the target protein InhA were compared with established anti-tubercular medicines (isoniazid and ethionamide). Based on docking results, the top furan chalcones were synthesized and analyzed using various spectroscopic techniques such as FT-IR, mass spectrometry, ¹H NMR, and ¹³C NMR. The synthesized chalcones were further investigated for their antitubercular efficacy using the Microplate Alamar Blue Assay (MABA) against the H37Rv strain. Among the tested compounds, DM01, DM02, DM03, DM04, DM05, and DM07 displayed optimum activity against H37Rv strain cell lines. Biocompatibility of synthesized top furan chalcone DMO3 was tested on mouse 3T3 fibroblast cells by cell viability or cytotoxicity assay. Phase contrast and live dead cells fluorescent staining assay used to determine the cytotoxicity. Tested compound was not recorded any sign of cytopathic effect which was confirmed by high rate of cell viability with complete absence of cytopathic effect and apoptosis. Further, the molecular docking studies identified the binding mechanism of reference drugs (isoniazid and ethionamide) with InhA, revealing key hydrogen-bond interactions with specific residues.