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Identification of some bioactive compounds from Trignonella foenumgraecum as possible inhibitors of PPARϒ for diabetes treatment through molecular docking studies, pharmacophore modelling and ADMET profiling: An in-silico study.
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.
Affiliation
  • Okoh OS; Department of Chemical Sciences, Anchor University, Lagos, Nigeria.
  • Yakubu A; Department of Pharmaceutical Chemistry, University of Maiduguri, Maiduguri, Nigeria.
  • Adegboyega AE; Department of Biochemistry, Faculty of Basic Medical Science, University of Jos, Jos, Nigeria.
  • Uti DE; Jaris Computational Biology Centre, Jos, Nigeria.
  • Obeten UN; Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, Federal University of Health Sciences, Otukpo, Benue State, Nigeria.
  • Agada SA; Department of Chemistry/Biochemistry and Molecular Biology, Alex Ekwueme Federal University, Ndufu-Alike Ikwo, Abakaliki, Ebonyi State, Nigeria.
  • Oluwaloni F; Department of Biochemistry, Faculty of Basic Medical Sciences, College of Medicine, Federal University of Health Sciences, Otukpo, Benue State, Nigeria.
  • Johnson GI; Department of Biotechnology, Federal Institute of Industrial Research, Oshodi, Lagos, Nigeria.
  • Mela LP; Jaris Computational Biology Centre, Jos, Nigeria.
  • Asomadu RO; Faculty of Medical Sciences, College of Health Sciences, University of Jos, Jos, Nigeria.
  • Iwaloye O; Department of Clinical Pharmacology and Therapeutics, College of Medical Sciences, University of Maiduguri, Maiduguri, Nigeria.
  • Johnson TO; University of Nigeria, Nnsuka, Nigeria.
  • Orji OU; Jaris Computational Biology Centre, Jos, Nigeria.
PLoS One ; 18(5): e0284210, 2023.
Article in En | MEDLINE | ID: mdl-37200359
Oral antidiabetic agents including the peroxisome proliferator-activated receptor gamma (PPARγ) 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 PPARγ; 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 PPARγ and are considered as antidiabetic agents after successful experimental validation.
Subject(s)

Full text: 1 Database: MEDLINE Therapeutic Methods and Therapies TCIM: Plantas_medicinales Main subject: Trigonella / Diabetes Mellitus Type of study: Diagnostic_studies / Prognostic_studies Language: En Journal: PLoS One Year: 2023 Type: Article Affiliation country: Nigeria

Full text: 1 Database: MEDLINE Therapeutic Methods and Therapies TCIM: Plantas_medicinales Main subject: Trigonella / Diabetes Mellitus Type of study: Diagnostic_studies / Prognostic_studies Language: En Journal: PLoS One Year: 2023 Type: Article Affiliation country: Nigeria