Antidiabetic Activity of Halogenated 2,4- Oxazolidinediones: Network Pharmacology, Molecular Docking and ADMET study

Abstract

Diabetes mellitus (DM) is a chronic metabolic disorder caused by inadequate secretion of insulin by pancreas or inadequate consumption of the secreted insulin by the body. About 422 million humans have diabetes and 1.5 million deaths are attributed to diabetes each year. Oxazolidine dione scaffolds are known for anticancer, antimicrobial, antibacterial, antioxidant, anticonvulsant and immune modulatory activities. In this study, we employed a comprehensive approach combining network pharmacology and molecular docking studies to explore the potential impact of halogenated oxazolidine diones on DM. A total of 58 compounds were retrieved from PubChem database and were subjected to physiochemical, pharmacokinetic, medicinal chemistry friendliness and toxicity profile using SwissADME and pkCSM webservers. The molecular targets of the retained compounds were identified using Swiss Target Prediction and DM were identified using GeneCards database. The common targets were used to establish protein-protein interaction (PPI) network and pathway enrichment analysis. Top 9 targets were identified using CytoHubba plugin in Cytoscape, among those, 2 targets, JAK2 and STAT3, were confirmed through disease enrichment pathway. Molecular docking was performed using Mz-Dock tool with Autodock vina mode. Molecular docking studies revealed that the compounds 5-(3-Chloro-2-methoxy- 5,6,7,8-tetrahydronaphthalen-1-yl)-1,3-oxazolidine-2,4-dione and 5-[5-Chloro-1- (cyclopropylmethyl)-6-methoxy-2,3-dihydroindol-7-yl]-1,3-oxazolidine-2,4-dione showed good binding energy and interaction profile. In conclusion, our study proposed that the identified key compounds contribute to the treatment of DM.