Synthesis, molecular docking, enzyme inhibition and antioxidant potential of new 1H-benzo[d]imidazole-5-carboxamide derivatives

Abstract

The therapeutic potential of benzimidazole has brought them widespread recognition as a class of heterocyclic compounds having nitrogen-containing rings. In recent years, there has been a lot of focus on synthesizing these molecules in order to reveal a broad range of biological actions. Therefore, a novel series of 1H-benzo[d]imidazole-5-carboxamide derivatives were designed, synthesized, and investigated for their antioxidant and enzyme inhibitory activities. The structural elucidation of synthesized compounds was accomplished by a variety of spectroscopic techniques, such as elemental analysis, 1H and 13C NMR, and LC-MS. Using the DPPH and FRAP techniques, the antioxidant activity of newly synthesized compounds was assessed. With IC50 values of 81.45, 72.14, and 77.35 µM, respectively, in the DPPH assay and 86.07, 75.02, and 81.14 µM, respectively, in the FRAP assay, the compounds 10c, 10f, and 10 g shown have significant antioxidant activity in comparisons with reference drugs ascorbic acid and Trolox. Furthermore, the inhibitory activity of xanthine oxidase (XO) and lipoxygenase (LOX) enzymes was assessed for the most potent molecules. Compounds 10c, 10f, and 10 g show superior inhibitory effects than reference drugs allopurinol and baicalein, with IC50 values of 19.52, 13.95, and 15.83 µM, respectively, against LOX and 26.14, 18.43, and 22.05 µM, respectively, against the XO enzyme. Moreover, studies using molecular docking were conducted to gain a deeper understanding of the interactions between the 3NM8 and 1N8Q protein and the most effective compounds, 10c, 10f, and 10 g. While compared to the reference medications, the studied compounds showed substantial docking scores and binding affinities, as indicated by docking studies. Through the use of drug-likeness and structure-activity relationships (SAR), an association between the newly synthesized compounds' biological and physicochemical properties was established.