AI Summary
This study focuses on the potential use of quinoline-based Schiff's base compounds as antidiabetic agents through α-glucosidase enzyme inhibition. The research includes ligand-based pharmacophore modeling, 3D QSAR model development, molecular docking, and molecular dynamic simulations to identify, synthesize, and characterize compounds. Compound 6c showed promising α-glucosidase inhibitory activity. Results indicate a competitive type of inhibition and a strong correlation in the QSAR model. The compounds displayed no toxicity in cell lines. Molecular docking studies and MD trajectory analysis were conducted to assess binding orientation and stability. Overall, the study provides valuable insights into the potential of quinoline-based compounds as antidiabetic agents.
α-glucosidase enzyme inhibition is a legitimate approach to combat type 2 Diabetes mellitus as it manages to control postprandial hyperglycemia. In this pursuit, a literature search identified quinoline-based molecules as potential α-glucosidase inhibitors. Thus our intended approach is to identify pharmacophoric features responsible for the α-glucosidase inhibition. This was achieved by performing, ligand-based pharmacophore modeling, 3D QSAR model development, pharmacophore-based screening of rationally designed quinoline-based benzohydrazide Schiff’s base library, identifying, synthesizing and characterizing the molecules (6a-6j) by IR, (1H and 13C) NMR, and mass studies. Further, these molecules were evaluated for α-glucosidase and α-amylase inhibitory potential. Compound 6c was found to be inhibiting α-glucosidase enzyme with an IC50 value of 12.95 ± 2.35 µM. Similarly, compound 6b was found to have an IC50 value of 19.37 ± 0.96 µM as compared to acarbose (IC50 :32.63 ± 1.07µM), inhibitory kinetic of the compounds 6b and 6c revealed a competitive type of inhibition, the inhibitory effect can be attributed to its mapped pharmacophoric feature and model validation with survival score of 5.0697 and vector score of 0.9552. QSAR model showed a strong correlation with an R2 value of 0.96. All the compounds (6a-6j) showed no toxicity in L929 cell lines by the MTT assay method. Further, the binding orientation and stability of the molecules were assessed using molecular docking studies and an MD trajectory analysis. The energy profile of the molecules with protein as a complex and molecules alone was evaluated using MM/GBSA and DFT calculations respectively, finally, the pharmacokinetic profile