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Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach

Glucokinase activators are considered as new therapeutic arsenals that bind to the allosteric activator sites of glucokinase enzymes, thereby maximizing its catalytic rate and increasing its affinity to glucose. This study was designed to identify potent glucokinase activators from prenylated flavon...

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Autores principales: Faloye, Kolade Olatubosun, Bekono, Boris Davy, Fakola, Emmanuel Gabriel, Ayoola, Marcus Durojaye, Bello, Oyenike Idayat, Olajubutu, Oluwabukunmi Grace, Owoseeni, Onikepe Deborah, Mahmud, Shafi, Alqarni, Mohammed, Al Awadh, Ahmed Abdullah, Alshahrani, Mohammed Merae, Obaidullah, Ahmad J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659159/
https://www.ncbi.nlm.nih.gov/pubmed/34885792
http://dx.doi.org/10.3390/molecules26237211
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author Faloye, Kolade Olatubosun
Bekono, Boris Davy
Fakola, Emmanuel Gabriel
Ayoola, Marcus Durojaye
Bello, Oyenike Idayat
Olajubutu, Oluwabukunmi Grace
Owoseeni, Onikepe Deborah
Mahmud, Shafi
Alqarni, Mohammed
Al Awadh, Ahmed Abdullah
Alshahrani, Mohammed Merae
Obaidullah, Ahmad J.
author_facet Faloye, Kolade Olatubosun
Bekono, Boris Davy
Fakola, Emmanuel Gabriel
Ayoola, Marcus Durojaye
Bello, Oyenike Idayat
Olajubutu, Oluwabukunmi Grace
Owoseeni, Onikepe Deborah
Mahmud, Shafi
Alqarni, Mohammed
Al Awadh, Ahmed Abdullah
Alshahrani, Mohammed Merae
Obaidullah, Ahmad J.
author_sort Faloye, Kolade Olatubosun
collection PubMed
description Glucokinase activators are considered as new therapeutic arsenals that bind to the allosteric activator sites of glucokinase enzymes, thereby maximizing its catalytic rate and increasing its affinity to glucose. This study was designed to identify potent glucokinase activators from prenylated flavonoids isolated from medicinal plants using molecular docking, molecular dynamics simulation, density functional theory, and ADMET analysis. Virtual screening was carried out on glucokinase enzymes using 221 naturally occurring prenylated flavonoids, followed by molecular dynamics simulation (100 ns), density functional theory (B3LYP model), and ADMET (admeSar 2 online server) studies. The result obtained from the virtual screening with the glucokinase revealed arcommunol B (−10.1 kcal/mol), kuwanon S (−9.6 kcal/mol), manuifolin H (−9.5 kcal/mol), and kuwanon F (−9.4 kcal/mol) as the top-ranked molecules. Additionally, the molecular dynamics simulation and MM/GBSA calculations showed that the hit molecules were stable at the active site of the glucokinase enzyme. Furthermore, the DFT and ADMET studies revealed the hit molecules as potential glucokinase activators and drug-like candidates. Our findings suggested further evaluation of the top-ranked prenylated flavonoids for their in vitro and in vivo glucokinase activating potentials.
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spelling pubmed-86591592021-12-10 Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach Faloye, Kolade Olatubosun Bekono, Boris Davy Fakola, Emmanuel Gabriel Ayoola, Marcus Durojaye Bello, Oyenike Idayat Olajubutu, Oluwabukunmi Grace Owoseeni, Onikepe Deborah Mahmud, Shafi Alqarni, Mohammed Al Awadh, Ahmed Abdullah Alshahrani, Mohammed Merae Obaidullah, Ahmad J. Molecules Article Glucokinase activators are considered as new therapeutic arsenals that bind to the allosteric activator sites of glucokinase enzymes, thereby maximizing its catalytic rate and increasing its affinity to glucose. This study was designed to identify potent glucokinase activators from prenylated flavonoids isolated from medicinal plants using molecular docking, molecular dynamics simulation, density functional theory, and ADMET analysis. Virtual screening was carried out on glucokinase enzymes using 221 naturally occurring prenylated flavonoids, followed by molecular dynamics simulation (100 ns), density functional theory (B3LYP model), and ADMET (admeSar 2 online server) studies. The result obtained from the virtual screening with the glucokinase revealed arcommunol B (−10.1 kcal/mol), kuwanon S (−9.6 kcal/mol), manuifolin H (−9.5 kcal/mol), and kuwanon F (−9.4 kcal/mol) as the top-ranked molecules. Additionally, the molecular dynamics simulation and MM/GBSA calculations showed that the hit molecules were stable at the active site of the glucokinase enzyme. Furthermore, the DFT and ADMET studies revealed the hit molecules as potential glucokinase activators and drug-like candidates. Our findings suggested further evaluation of the top-ranked prenylated flavonoids for their in vitro and in vivo glucokinase activating potentials. MDPI 2021-11-28 /pmc/articles/PMC8659159/ /pubmed/34885792 http://dx.doi.org/10.3390/molecules26237211 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Faloye, Kolade Olatubosun
Bekono, Boris Davy
Fakola, Emmanuel Gabriel
Ayoola, Marcus Durojaye
Bello, Oyenike Idayat
Olajubutu, Oluwabukunmi Grace
Owoseeni, Onikepe Deborah
Mahmud, Shafi
Alqarni, Mohammed
Al Awadh, Ahmed Abdullah
Alshahrani, Mohammed Merae
Obaidullah, Ahmad J.
Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach
title Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach
title_full Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach
title_fullStr Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach
title_full_unstemmed Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach
title_short Elucidating the Glucokinase Activating Potentials of Naturally Occurring Prenylated Flavonoids: An Explicit Computational Approach
title_sort elucidating the glucokinase activating potentials of naturally occurring prenylated flavonoids: an explicit computational approach
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659159/
https://www.ncbi.nlm.nih.gov/pubmed/34885792
http://dx.doi.org/10.3390/molecules26237211
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