Celebrex derivatives: Synthesis, α-glucosidase inhibition, crystal structures and molecular docking studies

[Display omitted] •Celebrex derivatives were synthesized as potent α-glucosidase inhibitors.•Celebrex analogue with 3′′′-nitro-4′′′-methyl substituents was the most active analogue (IC50 = 92.32 ± 1.53 µM).•Mode of inhibition of synthesized compounds was studied using enzyme kinetics.•Molecular docking studies of active compounds showed significant binding interactions with critical amino acid residues (His280, Tyr158, and Arg315) of enzyme. Celebrex (1), commonly used as an anti-inflammatory drug, was functionalized (compounds 2–9) to identify new α-glucosidase inhibitors. Initially, all the synthesized derivatives were evaluated for anti-inflammatory activity but none was found to be active. Subsequently a random biological screening was carried out. Interestingly many of them were found to be potent α-glucosidase inhibitors in vitro. All the structures of synthesized derivatives were deduced through 1H NMR, FAB-MS, HR-MS, FT-IR analysis. The single-crystal X-ray structures of compounds 1, and 5 further confirmed the assigned structures. Compounds exhibited a potent α-glucosidase inhibitory activity (IC50 = 92.32 ± 1.530–445.20 ± 1.04 µM) against tested standard acarbose (IC50 = 875.75 ± 2.08 µM), except compounds 2 and 4, which appeared as inactive. Among them, compound 9 (IC50 = 92.32 ± 1.530 µM) was the most potent inhibitor of α-glucosidase enzyme. Molecular docking studies revealed that compounds 6, and 9 interacted with the key amino acid residues of α-glucosidase via H-bonding, and π-π stacking interactions. α-Glucosidase is a key target for the anti-diabetic drug development, and its inhibitors are known to exert anti hyperglycemic effect and help in lowering of post-prandial blood glucose levels.