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.

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.

Protocol to identify multiple protein targets and therapeutic compounds using an in silico polypharmacological approach.

Polypharmacology aids in the identification of multiple protein targets involved in disease pathology and selecting appropriate therapeutic compounds interacting with protein targets. Here, we present a protocol to identify the targets involved in obesity-linked diabetes and suitable phytocompounds to bind with the identified target. We describe steps to install and use softwares for identifying several protein targets by linking multiple diseases. This protocol allows the use of therapeutic compounds of both phytochemical and synthetic origins. For complete details on the use and execution of this protocol, please refer to Martiz et al.,1 and Maradesha et al.2.

To Evaluate the Effect of Edrophonium on Blood Glucose Levels in Euglycemic Albino Rats Through OGTT.

OBJECTIVE: To evaluate the effect of Edrophonium on blood glucose levels in euglycemic albino rats through OGTT. MATERIALS AND METHODS: Twelve Swiss albino rats weighing around 150-200 gms of either sex were randomly selected from the central animal facility, JSSMC, Mysore and divided into two groups. The control group received distilled water (25ml/kg body wt.) per orally, test groups received Edrophonium (6.3mg/kg/day) intravenously for five days. On the fifth day, following overnight fasting, half an hour after drug administration in all the groups of rats Oral Glucose Tolerance Test was performed, by administering oral glucose in dose of 0.6gm/kg body weight. The capillary blood glucose levels were measured at 0, 60 and 150 min, by rat tail snipping method using (ACCUCHEK) glucometer. RESULTS: The Capillary Blood Glucose levels of Edrophonium group was less when compared to control group at all-time intervals. CONCLUSION: Edrophonium showed the hypoglycemic activity when given for five days intravenously in euglycemic albino rats through Oral Glucose Tolerance Test.