Staff View: Chromenone-based GSK-3ß inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles

Chromenone-based GSK-3ß inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles

Glycogen synthase kinase-3 beta (GSK-3ß) regulates glycogen metabolism and many different cellulars, including apoptosis, signaling, and neural. It is a crucial therapeutic receptor in heart disease, type 2 diabetes, and Alzheimer’s. In this study, using computational methods, flavonoid compounds we...

Full description

Saved in:

Bibliographic Details
Main Authors:	Min Zhang, San Zhou, Noor H. Obaid, Usama S. Altimari, Mohanad Adel Mohammed, Ahmed Kareem Obaid Aldulaim, Emad Salaam Abood, Hossam Kotb, Ayesheh Enayati, Vahid Khori, Hassan Mirzaei, Aref Salehi, Alireza Soltani, Mohd Sani Sarjadi, Md. Lutfor Rahman
Format:	Article
Language:	English English
Published:	Elsevier B.V. 2022
Subjects:	QD1-999 Chemistry R5-920 Medicine (General)
Online Access:	https://eprints.ums.edu.my/id/eprint/35099/1/ABSTRACT.pdf https://eprints.ums.edu.my/id/eprint/35099/2/FULL%20TEXT.pdf https://eprints.ums.edu.my/id/eprint/35099/ https://www.sciencedirect.com/science/article/pii/S1878535222006049 https://doi.org/10.1016/j.arabjc.2022.104288
Tags:	Add Tag No Tags, Be the first to tag this record!

id	my.ums.eprints.35099
record_format	eprints
spelling	my.ums.eprints.350992023-02-13T04:14:43Z https://eprints.ums.edu.my/id/eprint/35099/ Chromenone-based GSK-3ß inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles Min Zhang San Zhou Noor H. Obaid Usama S. Altimari Mohanad Adel Mohammed Ahmed Kareem Obaid Aldulaim Emad Salaam Abood Hossam Kotb Ayesheh Enayati Vahid Khori Hassan Mirzaei Aref Salehi Alireza Soltani Mohd Sani Sarjadi Md. Lutfor Rahman QD1-999 Chemistry R5-920 Medicine (General) Glycogen synthase kinase-3 beta (GSK-3ß) regulates glycogen metabolism and many different cellulars, including apoptosis, signaling, and neural. It is a crucial therapeutic receptor in heart disease, type 2 diabetes, and Alzheimer’s. In this study, using computational methods, flavonoid compounds were investigated for potential inhibitors against GSK-3ß. Virtual screening was utilized to investigate flavonoid compounds obtained from the PubChem database. Structure of human heart mitochondria of GSK-3ß receptor constructed by homology modeling. Best binding poses were discovered via in silico molecular docking simulation. We surveyed noncovalent interactions among amino acid residues involved in the active site of the modeled Protein and compounds via molecular docking and molecular dynamics (MD). Moreover, ADMET characteristics of best docking conformers have been investigated. The obtained results revealed that compound 1 containing chromenone moiety with binding energy H-bond -11.4 kcal/mol inhibited effectively binding pocket of the GSK-3ß receptor. Moreover, MD simulation analysis (RMSD and radius of gyration indicated complex of the compound and GSK-3b receptor remained stable throughout 100 ns MD simulation, and also analysis of ADMET profiles revealed that selected compounds had good drug-likeness and pharmacokinetic properties. Hence, it was suggested that compounds with chromenone scaffold could potentially inhibit GSK3ß. Structural modification of the chromenone derivatives may result in the discovery of promising candidates for identifying novel drugs as GSK-3ß inhibitors. Elsevier B.V. 2022 Article PeerReviewed text en https://eprints.ums.edu.my/id/eprint/35099/1/ABSTRACT.pdf text en https://eprints.ums.edu.my/id/eprint/35099/2/FULL%20TEXT.pdf Min Zhang and San Zhou and Noor H. Obaid and Usama S. Altimari and Mohanad Adel Mohammed and Ahmed Kareem Obaid Aldulaim and Emad Salaam Abood and Hossam Kotb and Ayesheh Enayati and Vahid Khori and Hassan Mirzaei and Aref Salehi and Alireza Soltani and Mohd Sani Sarjadi and Md. Lutfor Rahman (2022) Chromenone-based GSK-3ß inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles. Arabian Journal of Chemistry, 15 (104288). pp. 1-13. ISSN 1878-5352 (P-ISSN) , 1878-5379 (E-ISSN) https://www.sciencedirect.com/science/article/pii/S1878535222006049 https://doi.org/10.1016/j.arabjc.2022.104288
institution	Universiti Malaysia Sabah
building	UMS Library
collection	Institutional Repository
continent	Asia
country	Malaysia
content_provider	Universiti Malaysia Sabah
content_source	UMS Institutional Repository
url_provider	http://eprints.ums.edu.my/
language	English English
topic	QD1-999 Chemistry R5-920 Medicine (General)
spellingShingle	QD1-999 Chemistry R5-920 Medicine (General) Min Zhang San Zhou Noor H. Obaid Usama S. Altimari Mohanad Adel Mohammed Ahmed Kareem Obaid Aldulaim Emad Salaam Abood Hossam Kotb Ayesheh Enayati Vahid Khori Hassan Mirzaei Aref Salehi Alireza Soltani Mohd Sani Sarjadi Md. Lutfor Rahman Chromenone-based GSK-3ß inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles
description	Glycogen synthase kinase-3 beta (GSK-3ß) regulates glycogen metabolism and many different cellulars, including apoptosis, signaling, and neural. It is a crucial therapeutic receptor in heart disease, type 2 diabetes, and Alzheimer’s. In this study, using computational methods, flavonoid compounds were investigated for potential inhibitors against GSK-3ß. Virtual screening was utilized to investigate flavonoid compounds obtained from the PubChem database. Structure of human heart mitochondria of GSK-3ß receptor constructed by homology modeling. Best binding poses were discovered via in silico molecular docking simulation. We surveyed noncovalent interactions among amino acid residues involved in the active site of the modeled Protein and compounds via molecular docking and molecular dynamics (MD). Moreover, ADMET characteristics of best docking conformers have been investigated. The obtained results revealed that compound 1 containing chromenone moiety with binding energy H-bond -11.4 kcal/mol inhibited effectively binding pocket of the GSK-3ß receptor. Moreover, MD simulation analysis (RMSD and radius of gyration indicated complex of the compound and GSK-3b receptor remained stable throughout 100 ns MD simulation, and also analysis of ADMET profiles revealed that selected compounds had good drug-likeness and pharmacokinetic properties. Hence, it was suggested that compounds with chromenone scaffold could potentially inhibit GSK3ß. Structural modification of the chromenone derivatives may result in the discovery of promising candidates for identifying novel drugs as GSK-3ß inhibitors.
format	Article
author	Min Zhang San Zhou Noor H. Obaid Usama S. Altimari Mohanad Adel Mohammed Ahmed Kareem Obaid Aldulaim Emad Salaam Abood Hossam Kotb Ayesheh Enayati Vahid Khori Hassan Mirzaei Aref Salehi Alireza Soltani Mohd Sani Sarjadi Md. Lutfor Rahman
author_facet	Min Zhang San Zhou Noor H. Obaid Usama S. Altimari Mohanad Adel Mohammed Ahmed Kareem Obaid Aldulaim Emad Salaam Abood Hossam Kotb Ayesheh Enayati Vahid Khori Hassan Mirzaei Aref Salehi Alireza Soltani Mohd Sani Sarjadi Md. Lutfor Rahman
author_sort	Min Zhang
title	Chromenone-based GSK-3ß inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles
title_short	Chromenone-based GSK-3ß inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles
title_full	Chromenone-based GSK-3ß inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles
title_fullStr	Chromenone-based GSK-3ß inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles
title_full_unstemmed	Chromenone-based GSK-3ß inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles
title_sort	chromenone-based gsk-3ß inhibitors as potential therapeutic targets for cardiovascular diseases: in silico study, molecular dynamics, and admet profiles
publisher	Elsevier B.V.
publishDate	2022
url	https://eprints.ums.edu.my/id/eprint/35099/1/ABSTRACT.pdf https://eprints.ums.edu.my/id/eprint/35099/2/FULL%20TEXT.pdf https://eprints.ums.edu.my/id/eprint/35099/ https://www.sciencedirect.com/science/article/pii/S1878535222006049 https://doi.org/10.1016/j.arabjc.2022.104288
_version_	1760231383983194112
score	13.211869

Chromenone-based GSK-3ß inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles

Similar Items