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
Copyright: © 2023 Okoh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
PloS one - 18(2023), 5 vom: 31., Seite e0284210 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Okoh, Olayinka Sunday [VerfasserIn] |
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| Links: |
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| Themen: |
27YG812J1I |
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| Anmerkungen: |
Date Completed 23.05.2023 Date Revised 05.06.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0284210 |
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| 100 | 1 | |a Okoh, Olayinka Sunday |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a 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 |b An in-silico study |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Revised 05.06.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright: © 2023 Okoh et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a 27YG812J1I |2 NLM | |
| 650 | 7 | |a Hypoglycemic Agents |2 NLM | |
| 650 | 7 | |a Ligands |2 NLM | |
| 650 | 7 | |a PPAR gamma |2 NLM | |
| 700 | 1 | |a Yakubu, AbdulbasitHaliru |e verfasserin |4 aut | |
| 700 | 1 | |a Adegboyega, Abayomi Emmanuel |e verfasserin |4 aut | |
| 700 | 1 | |a Uti, Daniel Ejim |e verfasserin |4 aut | |
| 700 | 1 | |a Obeten, Uket Nta |e verfasserin |4 aut | |
| 700 | 1 | |a Agada, Samuel Ali |e verfasserin |4 aut | |
| 700 | 1 | |a Oluwaloni, Folusho |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Grace Inioluwa |e verfasserin |4 aut | |
| 700 | 1 | |a Mela, Leonard Paul |e verfasserin |4 aut | |
| 700 | 1 | |a Asomadu, Rita Onyekachukwu |e verfasserin |4 aut | |
| 700 | 1 | |a Iwaloye, Opeyemi |e verfasserin |4 aut | |
| 700 | 1 | |a Johnson, Titilayo Omolara |e verfasserin |4 aut | |
| 700 | 1 | |a Orji, Obasi Uche |e verfasserin |4 aut | |
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