Novel Furan Coupled Quinoline Diamide Hybrid Scaffolds as Potent Antitubercular Agents: Design, Synthesis and Molecular Modelling

Background: A novel series of 2-[(2-{[2-(furan-2-yl) quinolin-4-yl] carbonyl} hydrazinyl) carbonyl] benzoic acid, -4-oxobut-2-enoic acid and -4-oxobutanoic acids were synthesized and screened for in vitro antitubercular activity. Objectives: In the present investigation, we describe the synthesis and biological screening of furan C-2 quinoline coupled diamides for antitubercular activity. Methods: The mycobacterium tuberculai testing was carried out by MABA method and molecular docking studies were done by open-source molecular docking program, Autovina, using Pyrx 0.8 interface. Results: The results revealed that the compounds inhibited the growth of H37Rv strain at concentrations as low as 1.6 to 12 μg/ml. Molecular binding of furan, quinoline and diamide (FQD) derivatives on five targets was good and these compounds fit very well within the binding domain of the target protein. Conclusion: The synthesized FQD derivatives exhibited moderate to good inhibition activity especially compounds 5f, 5b and 8a exhibited very good inhibition activity due to the presence of three different scaffolds, such as INH, phenyl ketobutyric acid and fluoroquinolines. Hybridized molecules might have multiple modes of action / inhibit more than one tubercular target and could pave way for novel drug discovery in the field of tuberculosis.