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Benzimidazole scaffolds are known to have a diverse range of biological activities and found to be antidiabetic and antioxidant. In this study, a variety of arylated benzimidazoles 1–31 were synthesized. Except for compounds 1, 6, 7, and 8, all are new derivatives. All compounds were screened for α-amylase inhibitory, 2,2′-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), and 2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activities. In vitro screening results revealed that all molecules demonstrated significant α-amylase inhibition with IC50 values of 1.86 ± 0.08 to 3.16 ± 0.31 μM as compared to standard acarbose (IC50 = 1.46 ± 0.26 μM). However, compounds showed significant ABTS and DPPH radical scavenging potentials with IC50 values in the range of 1.37 ± 0.21 to 4.00 ± 0.10 μM for ABTS and 1.36 ± 0.09 to 3.60 ± 0.20 μM for DPPH radical scavenging activities when compared to ascorbic acid with IC50 values of 0.72 ± 0.21 and 0.73 ± 0.05 μM for ABTS and DPPH radical scavenging potentials, respectively. Structure–activity relationship (SAR) was established after critical analysis of varying substitution effects on α-amylase inhibitory and radical scavenging (ABTS and DPPH) potentials. However, molecular docking was also performed to figure out the active participation of different groups of synthetic molecules during binding with the active pocket of the α-amylase enzyme.

N-Aryl-3,4-dihydroisoquinoline carbothioamide analogues 1-22 were synthesized by a simple one-step reaction protocol and subjected to in vitro urease inhibition studies for the first time. All compounds 1-22 were found active and showed significant to moderate urease inhibitory potential. Specifically, analogues 1, 2, 4, and 7 were identified to be more potent (IC50 = 11.2 ± 0.81-20.4 ± 0.22 μM) than the standard thiourea (IC50 = 21.7 ± 0.34 μM). The structure-activity relationship showed that compounds bearing electron-donating groups showed superior activity. Molecular docking study on the most active derivatives revealed a good protein-ligand interaction profile against the corresponding target with key interactions, including hydrogen bonding, hydrophobic, and π-anion interactions.

(E)-3-(2-Benzylidenehydrazinyl)-5,6-diphenyl-1,2,4-triazines analogs 1–27 were synthesized by multi-step reaction scheme and subjected to in vitro inhibitory screening against α-amylase and α-glucosidase enzymes. Out of these twenty-seven synthetic analogs, ten compounds 14–17, 19, and 21–25 are structurally new. All compounds exhibited good to moderate inhibitory potential in terms of IC50 values ranging (IC50 = 13.02 ± 0.04–46.90 ± 0.05 µM) and (IC50 = 13.09 ± 0.08–46.44 ± 0.24 µM) in comparison to standard acarbose (IC50 = 12.94 ± 0.27 µM and 10.95 ± 0.08 µM), for α-amylase and α-glucosidase, respectively. Structure-activity relationship indicated that analogs with halogen substitution(s) were found more active as compared to compounds bearing other substituents. Kinetic studies on most active α-amylase and α-glucosidase inhibitors 5, 7, 9, 15, 24, and 27, suggested non-competitive and competitive types of inhibition mechanism for α-amylase and α-glucosidase, respectively. Molecular docking studies predicted the good protein-ligand interaction (PLI) profile with key interactions such as arene-arene, H

Dihydropyridine derivatives 1–31 were synthesized via one-pot solvent free condition and screened for in vitro against α-amylase and α-glucosidase enzyme. The synthetic derivatives 1–31 showed good α-amylase inhibition in the range of IC50 = 2.21 ± 0.06–9.97 ± 0.08 µM, as compared to the standard drug acarbose (IC50 = 2.01 ± 0.1 µM) and α-glucosidase inhibition in the range of IC50 = 2.31 ± 0.09–9.9 ± 0.1 µM as compared to standard acarbose (IC50 = 2.07 ± 0.1 µM), respectively. To determine the mode of binding interactions of synthetic molecules with active sites of enzyme, molecular docking studies were also performed. Different spectroscopic techniques such as 1H, 13C NMR, EI-MS, and HREI-MS were used to characterize all the synthetic compounds.

Inhibition of α-glucosidase enzyme is of prime importance for the treatment of diabetes mellitus (DM). Apart of many organic scaffolds, pyridine based compounds have previously been reported for wide range of bioactivities. The current study reports a series of pyridine based synthetic analogues for their α-glucosidase inhibitory potential assessed by in vitro, kinetics and in silico studies. For this purpose, 2-amino-4-aryl-6-(phenylthio)pyridine-3,5-dicarbonitriles 1–28 were synthesized and subjected to in vitro screening. Several analogs, including 1–3, 7, 9, 11–14, and 16 showed many folds increased inhibitory potential in comparison to the standard acarbose (IC50 = 750 ± 10 µM). Interestingly, compound 7 (IC50 = 55.6 ± 0.3 µM) exhibited thirteen-folds greater inhibition strength than the standard acarbose. Kinetic studies on most potent molecule 7 revealed a competitive type inhibitory mechanism. In silico studies have been performed to examine the binding mode of ligand (compound 7) with the active site residues of α-glucosidase enzyme.

5-Acetyl-6-methyl-4-aryl-3,4-dihydropyrimidin-2(1H)-ones 1-43 were synthesized in a "one-pot" three component reaction and structurally characterized by various spectroscopic techniques such as 1H, 13C NMR, EI-MS, HREI-MS, and IR. All compounds were evaluated for their in vitro urease inhibitory activity. It is worth mentioning that except derivatives 1, 11, 12, and 14, all were found to be more potent than the standard thiourea (IC50 = 21.25 ± 0.15 µM) and showed their urease inhibitory potential in the range of IC50 = 3.70 ± 0.5-20.14 ± 0.1 µM. Structure-activity relationship (SAR) was rationalized by looking at the varying structural features of the molecules. However, molecular modeling study was performed to confirm the binding interactions of the molecules (ligand) with the active site of enzyme.