Benzo[g]quinoline Derivatives as Potent α-Glucosidase Inhibitors: Synthesis, Characterization, and In Vitro Inhibition

Abstract Objective: Quinoline-fused heterocycles demonstrate various biological activities, including antibacterial, antifungal, anticancer and anti-inflammatory. However, their therapeutic potential in the context of diabetes remains underexplored. This research focuses on evaluating the α-glucosidase inhibitory potential of benzo[g]quinoline derivatives. Methods: An efficient synthetic route was established to generate a series of 3-((E)-((E)-benzylidene)hydrazineylidene)methyl)-2-chlorobenzo[g]quinoline derivatives 6a–6o. Structural elucidation of the newly synthesized compounds was performed using 1H and 13C NMR spectroscopy, FT-IR spectroscopy, mass spectrometry, and elemental analysis. The compounds were subsequently evaluated for their α-glucosidase inhibitory activity in vitro. Results and Discussion: All synthesized compounds exhibited α-glucosidase inhibitory activity. Notably, derivatives 6c, 6g, and 6h demonstrated significantly higher potency, with IC50 values of 16.40 ± 0.60, 6.80 ± 0.20, and 9.60 ± 0.30 µM, respectively, compared to the standard drug acarbose (IC50 = 38.45 ± 0.80 µM). Conclusions: The findings highlight the promising therapeutic potential of benzo[g]quinoline derivatives as α-glucosidase inhibitors, warranting further investigation for the management of diabetes.