Discovery of Novel Coumarin Derivatives as Potential Dual Inhibitors against α-Glucosidase and α-Amylase for the Management of Post-Prandial Hyperglycemia via Molecular Modelling Approaches

Abstract

Coumarin derivatives are proven for their therapeutic uses in several human diseases and disorders such as inflammation, neurodegenerative disorders, cancer, fertility, and microbial infections. Coumarin derivatives and coumarin-based scaffolds gained renewed attention for treating diabetes mellitus. The current decade witnessed the inhibiting potential of coumarin derivatives and coumarin-based scaffolds against α-glucosidase and α-amylase for the management of postprandial hyperglycemia. Hyperglycemia is a condition where an excessive amount of glucose circulates in the bloodstream. It occurs when the body lacks enough insulin or is unable to correctly utilize it. With open-source and free in silico tools, we have investigated novel 80 coumarin derivatives for their inhibitory potential against α-glucosidase and α-amylase and identified a coumarin derivative, CD-59, as a potential dual inhibitor. The ligand-based 3D pharmacophore detection and search is utilized to discover diverse coumarin-like compounds and new chemical scaffolds for the dual inhibition of α-glucosidase and α-amylase. In this regard, four novel coumarin-like compounds from the ZINC database have been discovered as the potential dual inhibitors of α-glucosidase and α-amylase (ZINC02789441 and ZINC40949448 with scaffold thiophenyl chromene carboxamide, ZINC13496808 with triazino indol thio phenylacetamide, and ZINC09781623 with chromenyl thiazole). To summarize, we propose that a coumarin derivative, CD-59, and ZINC02789441 from the ZINC database will serve as potential lead molecules with dual inhibition activity against α-glucosidase and α-amylase, thereby discovering new drugs for the effective management of postprandial hyperglycemia. From the reported scaffold, the synthesis of several novel compounds can also be performed, which can be used for drug discovery.

Phyto-Computational Intervention of Diabetes Mellitus at Multiple Stages Using Isoeugenol from Ocimum tenuiflorum: A Combination of Pharmacokinetics and Molecular Modelling Approaches

“…Furthermore, blood glucose levels that are too high cause a significant flow of glucose into the polyol pathway, where it is converted to sorbitol by aldose reductase [ 5 ]. Because the metabolism is impaired by the enzyme sorbitol dehydrogenase, sorbitol accumulates in the kidneys, nerves, and retina in diabetes patients.…”

Integrated network pharmacology and molecular modeling approach for the discovery of novel potential MAPK3 inhibitors from whole green jackfruit flour targeting obesity-linked diabetes mellitus

“…The virtual screening of the compounds was completed with a command-line-based software known as AutoDock Vina 1.1.2. It uses the Broyden-Fletcher-Goldfarb-Shanno (BGFS) algorithm to perturb and allocate ligands into the target site, and analyses the scoring function of each ligand conformation [ 27 ]. Because of the large number of torsions produced during ligand formation, ligands were considered to be flexible throughout the docking simulation, whereas protein was assumed to be rigid.…”

Pyrazole‐Imidazopyridine Hydrazones: Synthesis, α‐Glucosidase, α‐Amylase Inhibitory Activity and Computational Studies

“…In a previous study by the authors, [53,54] the protein and ligand structures were both prepared for the molecular docking simulation using AutoDock Tools 1.5.6. Water and heteroatoms were removed from the protein structures for purification.…”