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

Abstract

Polyhydroquinoline derivatives (1-15) 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 (1-15) were deduced through different spectroscopic techniques such as 1H NMR, 13C NMR, and HR–ESI–MS. The synthesized products were tested for their α-glucosidase inhibitory activity where compounds 11 (IC50 = 0.56 ± 0.01 μM), 10 (IC50 = 0.94 ± 0.01 μM), 4 (IC50 = 1.47 ± 0.01 μM), 2 (IC50 = 2.20 ± 0.03 μM), 6 (IC50 = 2.20 ± 0.03 μM), 12 (IC50 = 2.22 ± 0.07 μM), 7 (IC50 = 2.76 ± 0.04 μM), 9 (IC50 = 2.78 ± 0.03 μM), and 3 (IC50 = 2.88 ± 0.05 μM) exhibited high potential for the inhibition of α-glucosidase, while the rest of the compounds (8, 5, 14, 15, and 13) showed significant α-glucosidase inhibitory potential with IC50 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., 11 and 10, showed potent α-glucosidase inhibitory potential higher than the standard. All the compounds were compared with standard drug “acarbose” (IC50 = 873.34 ± 1.67 μM). An in silico method was used to predict their mode of binding within the active site of enzyme to understand their mechanism of inhibition. Our in silico observation complements with the experimental results.

Investigating Novel Thiophene Carbaldehyde Based Thiazole Derivatives as Potential Hits for Diabetic Management: Synthesis, In Vitro and In Silico Approach

“…[36,37] Controlling the catalytic activity of the enzyme αglucosidase (EC.3.2.1.20), located in the small intestine, is one strategy for treating this condition. [38,39] The α-1-4 bond linkage in starch or oligosaccharides is broken down by this enzyme into monosaccharides like glucose. [40,41] Therefore, α-glucosidase suppression can aid in preventing post-prandial hyperglycemia and its related consequences.…”

“…Improved treatments for this chronic illness are urgently needed because it is predicted that 300 million individuals worldwide would have diabetes mellitus by the year 2025 [36,37] . Controlling the catalytic activity of the enzyme α‐glucosidase (EC.3.2.1.20), located in the small intestine, is one strategy for treating this condition [38,39] . The α‐1‐4 bond linkage in starch or oligosaccharides is broken down by this enzyme into monosaccharides like glucose [40,41] .…”

Synthesis, molecular docking and DFT analysis of novel bis-Schiff base derivatives with thiobarbituric acid for α-glucosidase inhibition assessment

“…This structural knowledge becomes particularly relevant in the context of diabetes mellitus (DM), a chronic endocrine disease that significantly influences the regulation of glucose, electrolytes, fats, proteins, and water metabolism 26 , 27 . This disorder fits to a class of metabolic disorders described by hyperglycemia, reducing from inadequate insulin production by the pancreas or insufficient cellular receptiveness to insulin 28 , 29 .…”

“Synergistic Innovation: Crafting Indazole Derivatives for Advanced Anticancer, Antioxidant, and Antimicrobial Efficacy through Integrative Design and Holistic Evaluation”

“…In cancer, where normal apoptotic mechanisms are often subverted, allowing malignant cells to evade this natural control against unbridled growth, indazoles, through precise molecular interactions, have the potential to reinstate apoptosis in cancer cells. This, in turn, has the potential to curtail their survival and proliferation [38–40] …”