Novel 5-(Arylideneamino)-1 H-Benzo[ d]imidazole-2-thiols as Potent Anti-Diabetic Agents: Synthesis, in Vitro α-Glucosidase Inhibition, and Molecular Docking Studies

Abstract

A novel series of multifunctional benzimidazoles has been reported as potent inhibitors of α-glucosidase. The procedure relies on the synthesis of 5-amino-1H-benzo[d]imidazole-2-thiol 5 via the multistep reaction through 2-nitroaniline 1, benzene-1,2-diamine 2, 1H-benzo[d]imidazole-2-thiol 3, and 5-nitro-1H-benzo[d]imidazole-2-thiol 4. Further treatment of 5 with aromatic aldehydes 6a-m provided access to the target 5-(arylideneamino)-1H-benzo[d]imidazole-2-thiols 7a-m. The results of the bioactivity assessment revealed all the compounds as excellent inhibitors of the enzyme (IC50 range: 0.64 ± 0.05 μM to 343.10 ± 1.62 μM) than acarbose (873.34 ± 1.21). Among them, 7i was the most active inhibitor (IC50: 0.64 ± 0.05 μM) followed by 7d (IC50: 5.34 ± 0.16 μM), 7f (IC50: 6.46 ± 0.30 μM), 7g (IC50: 8.62 ± 0.19 μM), 7c (IC50: 9.84 ± 0.08 μM), 7m (IC50: 11.09 ± 0.79 μM), 7a (IC50: 11.84 ± 0.26 μM), 7e (IC50: 16.38 ± 0.53 μM), 7j (IC50: 18.65 ± 0.74 μM), 7h (IC50: 20.73 ± 0.59 μM), 7b (IC50: 27.26 ± 0.30 μM), 7k (70.28 ± 1.52 μM) and finally 7l (IC50: 343.10 ± 1.62 μM). Molecular docking revealed important interactions with the enzyme, thereby supporting the experimental findings.