Green synthesis, antimycobacterial evaluation and molecular docking studies of novel 2,3-dihydro-1H-pyrazol-4-ylnaphthalene-1,4-diones

•Novel 2,3-dihydro-1H-pyrazol-4-ylnaphthalene-1,4-diones (5a-j) demonstrated good to better in vitro antimycobacterial activity.•Molecular docking of compounds (5a-j) indicated noteworthy inhibitory activity against mycobacterium tuberculosis.•In-silico analysis predicted compounds (5a-j) to be safer therapeutics. A novel series of 2,3-dihydro-1H-pyrazol-4-ylnaphthalene-1,4-diones is synthesized via one-pot, multi-component condensation of ethyl acetoacetate, 4-(trifluoromethyl)phenylhydrazine, aromatic aldehydes and 7-fluoro-2-hydroxynaphthalene-1,4‑dione in aqueous p-toluenesulfonic acid (15 mol%) at 100 °C. The synthesized compounds (5a-j) were evaluated for their in vitro antimycobacterial efficacy against drug-sensitive and isoniazid-resistant Mycobacterium tuberculosis (Mtb) H37Rv strains using the broth based method. All compounds displayed good to better antimycobacterial activity with MIC values ranging from 0.49 to 5.16 µM. Compound 5i (MIC = 0.49±0.08 μM) demonstrated equivalent antimycobacterial activity as that of the reference drug isoniazid (MIC = 0.35±0.06 μM). Molecular docking of the synthesized compounds 5a-j with an active site of membrane transporter MmpL3 protein (PDB ID: 6AJJ) was performed to justify the results of in vitro antimycobacterial activity and offer insight into the possible mode of action and binding interaction of compounds with the receptor protein. Molecular descriptors and drug-like features of novel 2,3-dihydro-1H-pyrazol-4-ylnaphthalene-1,4-diones were also examined. [Display omitted]