Chromenone-based GSK-3β inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles
Glycogen synthase kinase-3 beta (GSK-3β) 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 compoun...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-12-01
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| Series: | Arabian Journal of Chemistry |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1878535222006049 |
| _version_ | 1798015593664741376 |
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| 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 |
| collection | DOAJ |
| description | Glycogen synthase kinase-3 beta (GSK-3β) 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-3β. Virtual screening was utilized to investigate flavonoid compounds obtained from the PubChem database. Structure of human heart mitochondria of GSK-3β 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-3β receptor. Moreover, MD simulation analysis (RMSD and radius of gyration indicated complex of the compound and GSK-3β 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 GSK-3β. Structural modification of the chromenone derivatives may result in the discovery of promising candidates for identifying novel drugs as GSK-3β inhibitors. |
| first_indexed | 2024-04-11T15:37:11Z |
| format | Article |
| id | doaj.art-b22996f1e7594f29b2e9425791bdb43a |
| institution | Directory Open Access Journal |
| issn | 1878-5352 |
| language | English |
| last_indexed | 2024-04-11T15:37:11Z |
| publishDate | 2022-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Arabian Journal of Chemistry |
| spelling | doaj.art-b22996f1e7594f29b2e9425791bdb43a2022-12-22T04:15:56ZengElsevierArabian Journal of Chemistry1878-53522022-12-011512104288Chromenone-based GSK-3β inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profilesMin Zhang0San Zhou1Noor H. Obaid2Usama S. Altimari3Mohanad Adel Mohammed4Ahmed Kareem Obaid Aldulaim5Emad Salaam Abood6Hossam Kotb7Ayesheh Enayati8Vahid Khori9Hassan Mirzaei10Aref Salehi11Alireza Soltani12Mohd Sani Sarjadi13Md. Lutfor Rahman14Department of Pharmacognosy, School of Pharmacy, Qingdao University, Qingdao, Shandong 266071, ChinaDepartment of Pharmacognosy, School of Pharmacy, Qingdao University, Qingdao, Shandong 266071, China; Corresponding authors.Anesthesia Techniques Department, Al-Mustaqbal University College, Babylon, IraqAl-Nisour University College, Baghdad, IraqCollege of Pharmacy, Al Farahidi University, Baghdad, IraqDepartment of Pharmacy, Al-Zahrawi University College, Karbala, IraqMedical Physics Department, Hilla University College, Babylon, IraqDepartment of Electrical Power and Machines, Faculty of Engineering, Alexandria University, Alexandria, EgyptIschemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, IranIschemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, IranIschemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran; Corresponding authors.Ischemic Disorders Research Center, Golestan University of Medical Sciences, Gorgan, Iran; Corresponding authors.Golestan Rheumatology Research Center, Golestan University of Medical Science, Gorgan, IranFaculty of Science and Natural Resources, Universiti Malaysia Sabah, Kota Kinabalu 88400, Sabah, MalaysiaFaculty of Science and Natural Resources, Universiti Malaysia Sabah, Kota Kinabalu 88400, Sabah, Malaysia; Corresponding authors.Glycogen synthase kinase-3 beta (GSK-3β) 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-3β. Virtual screening was utilized to investigate flavonoid compounds obtained from the PubChem database. Structure of human heart mitochondria of GSK-3β 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-3β receptor. Moreover, MD simulation analysis (RMSD and radius of gyration indicated complex of the compound and GSK-3β 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 GSK-3β. Structural modification of the chromenone derivatives may result in the discovery of promising candidates for identifying novel drugs as GSK-3β inhibitors.http://www.sciencedirect.com/science/article/pii/S1878535222006049GSK-3βChromenoneVirtual screeningMolecular dynamics simulationADMET |
| spellingShingle | 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-3β inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles Arabian Journal of Chemistry GSK-3β Chromenone Virtual screening Molecular dynamics simulation ADMET |
| title | Chromenone-based GSK-3β inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles |
| title_full | Chromenone-based GSK-3β inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles |
| title_fullStr | Chromenone-based GSK-3β inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles |
| title_full_unstemmed | Chromenone-based GSK-3β inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles |
| title_short | Chromenone-based GSK-3β inhibitors as potential therapeutic targets for cardiovascular diseases: In silico study, molecular dynamics, and ADMET profiles |
| title_sort | chromenone based gsk 3β inhibitors as potential therapeutic targets for cardiovascular diseases in silico study molecular dynamics and admet profiles |
| topic | GSK-3β Chromenone Virtual screening Molecular dynamics simulation ADMET |
| url | http://www.sciencedirect.com/science/article/pii/S1878535222006049 |
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