QSAR, ADME-Tox, molecular docking and molecular dynamics simulations of novel selective glycine transporter type 1 inhibitors with memory enhancing properties
A structural class of forty glycine transporter type 1 (GlyT1) inhibitors, was examined using molecular modeling techniques. The quantitative structure-activity relationships (QSAR) technology confirmed that human GlyT1 activity is strongly and significantly affected by constitutional, geometrical,...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | Heliyon |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023009131 |
| _version_ | 1811161703063224320 |
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| author | Mohamed El fadili Mohammed Er-rajy Hamada Imtara Omar M. Noman Ramzi A. Mothana Sheaf Abdullah Sara Zerougui Menana Elhallaoui |
| author_facet | Mohamed El fadili Mohammed Er-rajy Hamada Imtara Omar M. Noman Ramzi A. Mothana Sheaf Abdullah Sara Zerougui Menana Elhallaoui |
| author_sort | Mohamed El fadili |
| collection | DOAJ |
| description | A structural class of forty glycine transporter type 1 (GlyT1) inhibitors, was examined using molecular modeling techniques. The quantitative structure-activity relationships (QSAR) technology confirmed that human GlyT1 activity is strongly and significantly affected by constitutional, geometrical, physicochemical and topological descriptors. ADME-Tox in-silico pharmacokinetics revealed that L28 and L30 ligands were predicted as non-toxic inhibitors with a good ADME profile and the highest probability to penetrate the central nervous system (CNS). Molecular docking results indicated that the predicted inhibitors block GlyT1, reacting specifically with Phe319, Phe325, Tyr123, Tyr 124, Arg52, Asp475, Ala117, Ala479, Ile116 and Ile483 amino acids of the dopamine transporter (DAT) membrane protein. These results were qualified and strengthened using molecular dynamics (MD) study, which affirmed that the established intermolecular interactions for (L28, L30–DAT protein) complexes remain perfectly stable along 50 ns of MD simulation time. Therefore, they could be strongly recommended as therapeutics in medicine to improve memory performance. |
| first_indexed | 2024-04-10T06:19:39Z |
| format | Article |
| id | doaj.art-8f3bfe2bd2fb4120870ba96a5e6c9d20 |
| institution | Directory Open Access Journal |
| issn | 2405-8440 |
| language | English |
| last_indexed | 2024-04-10T06:19:39Z |
| publishDate | 2023-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Heliyon |
| spelling | doaj.art-8f3bfe2bd2fb4120870ba96a5e6c9d202023-03-02T05:02:34ZengElsevierHeliyon2405-84402023-02-0192e13706QSAR, ADME-Tox, molecular docking and molecular dynamics simulations of novel selective glycine transporter type 1 inhibitors with memory enhancing propertiesMohamed El fadili0Mohammed Er-rajy1Hamada Imtara2Omar M. Noman3Ramzi A. Mothana4Sheaf Abdullah5Sara Zerougui6Menana Elhallaoui7LIMAS Laboratory, Faculty of Sciences Dhar El Mehraz, Sidi Mohammed Ben Abdellah University, BP 1796 Atlas, Fez 30000, Morocco; Corresponding author.LIMAS Laboratory, Faculty of Sciences Dhar El Mehraz, Sidi Mohammed Ben Abdellah University, BP 1796 Atlas, Fez 30000, MoroccoFaculty of Arts and Sciences, Arab American University Palestine, Jenin BP Box 240, PalestineDepartment of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Pharmacognosy, College of Pharmacy, King Saud University, Riyadh 11451, Saudi ArabiaDepartment of Hand Surgery and Microsurgery, University Medicine Greifswald, Greifswald, GermanyLIMAS Laboratory, Faculty of Sciences Dhar El Mehraz, Sidi Mohammed Ben Abdellah University, BP 1796 Atlas, Fez 30000, MoroccoLIMAS Laboratory, Faculty of Sciences Dhar El Mehraz, Sidi Mohammed Ben Abdellah University, BP 1796 Atlas, Fez 30000, MoroccoA structural class of forty glycine transporter type 1 (GlyT1) inhibitors, was examined using molecular modeling techniques. The quantitative structure-activity relationships (QSAR) technology confirmed that human GlyT1 activity is strongly and significantly affected by constitutional, geometrical, physicochemical and topological descriptors. ADME-Tox in-silico pharmacokinetics revealed that L28 and L30 ligands were predicted as non-toxic inhibitors with a good ADME profile and the highest probability to penetrate the central nervous system (CNS). Molecular docking results indicated that the predicted inhibitors block GlyT1, reacting specifically with Phe319, Phe325, Tyr123, Tyr 124, Arg52, Asp475, Ala117, Ala479, Ile116 and Ile483 amino acids of the dopamine transporter (DAT) membrane protein. These results were qualified and strengthened using molecular dynamics (MD) study, which affirmed that the established intermolecular interactions for (L28, L30–DAT protein) complexes remain perfectly stable along 50 ns of MD simulation time. Therefore, they could be strongly recommended as therapeutics in medicine to improve memory performance.http://www.sciencedirect.com/science/article/pii/S2405844023009131QSARGlyT1ADME-ToxCNSDATMolecular docking |
| spellingShingle | Mohamed El fadili Mohammed Er-rajy Hamada Imtara Omar M. Noman Ramzi A. Mothana Sheaf Abdullah Sara Zerougui Menana Elhallaoui QSAR, ADME-Tox, molecular docking and molecular dynamics simulations of novel selective glycine transporter type 1 inhibitors with memory enhancing properties Heliyon QSAR GlyT1 ADME-Tox CNS DAT Molecular docking |
| title | QSAR, ADME-Tox, molecular docking and molecular dynamics simulations of novel selective glycine transporter type 1 inhibitors with memory enhancing properties |
| title_full | QSAR, ADME-Tox, molecular docking and molecular dynamics simulations of novel selective glycine transporter type 1 inhibitors with memory enhancing properties |
| title_fullStr | QSAR, ADME-Tox, molecular docking and molecular dynamics simulations of novel selective glycine transporter type 1 inhibitors with memory enhancing properties |
| title_full_unstemmed | QSAR, ADME-Tox, molecular docking and molecular dynamics simulations of novel selective glycine transporter type 1 inhibitors with memory enhancing properties |
| title_short | QSAR, ADME-Tox, molecular docking and molecular dynamics simulations of novel selective glycine transporter type 1 inhibitors with memory enhancing properties |
| title_sort | qsar adme tox molecular docking and molecular dynamics simulations of novel selective glycine transporter type 1 inhibitors with memory enhancing properties |
| topic | QSAR GlyT1 ADME-Tox CNS DAT Molecular docking |
| url | http://www.sciencedirect.com/science/article/pii/S2405844023009131 |
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