Identification of some bioactive compounds from Trignonella foenumgraecum as possible inhibitors of PPAR.sub.Ï for diabetes treatment through molecular docking studies, pharmacophore modelling and ADMET profiling: An in-silico study

• Published in: PloS one Vol. 18; no. 5; p. e0284210
• Main Authors: Okoh, Olayinka Sunday, Yakubu, AbdulbasitHaliru, Adegboyega, Abayomi Emmanuel, Uti, Daniel Ejim, Obeten, Uket Nta, Agada, Samuel Ali, Oluwaloni, Folusho, Johnson, Grace Inioluwa, Mela, Leonard Paul, Asomadu, Rita Onyekachukwu, Iwaloye, Opeyemi, Johnson, Titilayo Omolara, Orji, Obasi Uche
• Format: Journal Article
• Language: English
• Published: Public Library of Science 18-05-2023
• Subjects: Amino acids; Biological products; Care and treatment; Complications and side effects; Diabetes; Diabetes therapy; Diagnosis; Drug therapy; Force and energy; Hydrogen; Hypoglycemic agents; Patient outcomes; Properties; Protein binding; Saturated fatty acids; Nigeria
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0284210

Oral antidiabetic agents including the peroxisome proliferator-activated receptor gamma (PPAR[gamma]) agonists are available for the clinical management of diabetes mellitus (DM) but most are characterized by many adverse effects. In this study, we explore the antidiabetic properties of phytoconstituents from Trigonellafeonumgraecum (Fabaceae) as potential agonist of PPAR[gamma]; using in silico molecular docking, molecular mechanics generalized surface area (MM/GBSA)free binding energy prediction, Pharmacophore modeling experiment, and Pharmacokinetic/ toxicity analysis. One hundred and forty (140) compounds derived from Trigonellafeonumgraecum were screened by molecular docking against protein target PDB 3VI8. Results obtained from binding affinity (BA) and that of binding free energy (BFE) revealed five 5 compounds; arachidonic acid (CID_10467, BA -10.029, BFE -58.9), isoquercetin (CID_5280804, BA -9.507kcal/mol, BFE -56.33), rutin (CID_5280805, BA -9.463kcal/mol, BFE -56.33), quercetin (CID_10121947, BA -11.945kcal/mol, BFE -45.89) and (2S)-2-[[4-methoxy-3-[(pyrene-1-carbonylamino)methyl]phenyl]methyl]butanoic acid (CID_25112371, BA -10.679kcal/mol, BFE -45.73); and were superior to the standard; Rosiglitazone with a docking score of -7.672. Hydrogen bonding was notable in the protein-ligand complex interaction, with hydrophobic bond, polar bond and pipi stacking also observed. Their Pharmacokinetic/ toxicity profile showed varying druggable characteristics, but; arachidonic acid had the most favorable characteristics. These compounds are potential agonists of PPAR[gamma] and are considered as antidiabetic agents after successful experimental validation.