Bio-Oriented Synthesis of Novel Polyhydroquinoline Derivatives as α-Glucosidase Inhibitor for Management of Diabetes.

Polyhydroquinoline derivatives () were synthesized through an unsymmetrical Hantzsch reaction in excellent yields by treating 3,5-dibromo-4-hydroxybenzaldehyde, dimedone, ammonium acetate, and ethyl acetoacetate in ethanol solvent. The structures of the synthesized compounds () were deduced through different spectroscopic techniques such as H NMR, C NMR, and HR-ESI-MS. The synthesized products were tested for their α-glucosidase inhibitory activity where compounds (IC 0.56 ± 0.01 μM), (IC 0.94 ± 0.01 μM), (IC 1.47 ± 0.01 μM), (IC 2.20 ± 0.03 μM), (IC 2.20 ± 0.03 μM), (IC 2.22 ± 0.07 μM), (IC 2.76 ± 0.04 μM), (IC 2.78 ± 0.03 μM), and (IC 2.88 ± 0.05 μM) exhibited high potential for the inhibition of α-glucosidase, while the rest of the compounds (, , , , and ) showed significant α-glucosidase inhibitory potential with IC values of 3.13 ± 0.10, 3.34 ± 0.06, 4.27 ± 0.13, 6.34 ± 0.15, and 21.37 ± 0.61 μM, respectively. Among the synthesized series, two compounds, i.e., and , showed potent α-glucosidase inhibitory potential higher than the standard. All the compounds were compared with standard drug "acarbose" (IC = 873.34 ± 1.67 μM). An method was used to predict their mode of binding within the active site of enzyme to understand their mechanism of inhibition. Our observation complements with the experimental results.