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

A novel series of multifunctional benzimidazoles has been reported as potent inhibitors of a-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 mu M to 343.10 +/- 1.62 mu M) than acarbose (873.34 +/- 1.21). Among them, 7i was the most active inhibitor (IC50: 0.64 +/- 0.05 mu M) followed by 7d (IC50: 5.34 +/- 0.16 mu M), 7f (IC50: 6.46 +/- 0.30 mu M), 7g (IC50: 8.62 +/- 0.19 mu M), 7c (IC50: 9.84 +/- 0.08 mu M), 7m (IC50: 11.09 +/- 0.79 mu M), 7a (IC50: 11.84 +/- 0.26 mu M), 7e (IC50: 16.38 +/- 0.53 mu M), 7j (IC50: 18.65 +/- 0.74 mu M), 7h (IC50: 20.73 +/- 0.59 mu M), 7b (IC50: 27.26 +/- 0.30 mu M), 7k (70.28 +/- 1.52 mu M) and finally 7l (IC50: 343.10 +/- 1.62 mu M). Molecular docking revealed important interactions with the enzyme, thereby supporting the experimental findings.