Synthesis and biological evaluation of diclofenac acid derivatives as potential lipoxygenase and α-glucosidase inhibitors.

Inflammation is a complex physiological response associated with the onset and progression of various disorders, including diabetes. In this study, we synthesized a series of diclofenac acid derivatives and evaluated their potential anti-diabetic and anti-inflammatory activities. The compounds were specifically assessed for their ability to inhibit 15-lipoxygenase (15-LOX) and α-glucosidase enzymes. The structures of synthesized derivatives were confirmed through H nuclear magnetic resonance (NMR), C-NMR and high-resolution mass spectrometry (electron ionization) analysis. All these synthesized derivatives exhibited varying degrees of inhibitory activity against LOX, when compared with standard drugs, compounds (half-maximal inhibitory concentration (IC) 14 ± 1 µM), (IC 61 ± 1 µM) and (IC 67 ± 1 µM) showed good activity against the LOX enzyme. While the α-glucosidase inhibitory results revealed that most of the compounds exhibited significant activity when compared with the standard drug acarbose (376 ± 1 µM). The most potent compounds as αglucosidase inhibitors were (3 ± 1 µM), (5 ± 1 µM), (7 ± 1 µM) and (11 ± 1 µM). All these active compounds were found to be least toxic and maintained the mononuclear cells viability at 96-97% compared with that of controls as determined by multi-transaction translator assay. Molecular docking studies further reiterated the significance of these 'lead' compounds with great potential against the target enzymes in the process of drug discovery.