Discovery of thymol-fused chalcones as new competitive \(\alpha\)-glucosidase inhibitors: Design, synthesis, biological evaluation, and molecular modeling studies
This study aims to synthesize and evaluate the inhibitory activity of thymol derivatives targeting ?-glucosidase using in vitro and in silico studies. Ten thymol derivatives (2-11) including five new thymol-fused chalcones (7-11) were successfully synthesized. Among them, four compounds (4, 8, 9, 11...
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Komunitas Ilmuwan dan Profesional Muslim Indonesia
2024-12-01
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| Series: | Communications in Science and Technology |
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| Online Access: | https://cst.kipmi.or.id/journal/article/view/1497 |
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| author | Ade Danova Elvira Hermawati Warinthorn Chavasiri Didin Mujahidin Anita Alni Robby Roswanda |
| author_facet | Ade Danova Elvira Hermawati Warinthorn Chavasiri Didin Mujahidin Anita Alni Robby Roswanda |
| author_sort | Ade Danova |
| collection | DOAJ |
| description | This study aims to synthesize and evaluate the inhibitory activity of thymol derivatives targeting ?-glucosidase using in vitro and in silico studies. Ten thymol derivatives (2-11) including five new thymol-fused chalcones (7-11) were successfully synthesized. Among them, four compounds (4, 8, 9, 11) showed the best inhibitory activity with IC50 values of 18.45, 13.75, 8.86, and 10.67µM compared with acarbose (IC50 = 832.82 µM), respectively. The kinetic study of three new thymol-fused chalcones (8, 9, 11) exhibited a competitive inhibition. Molecular docking demonstrated the predicted interactions between ligand (8, 9, 11) and ?-glucosidase, which are responsible for inhibiting the enzyme's catalytic abilities. Furthermore, molecular dynamics simulation of the enzyme-ligand 9 complex indicated that this complex was stable in aqueous condition. This research contributes significantly to the understanding of thymol-fused chalcones that may have therapeutic potential and their possible application in the treatment of type 2 diabetes mellitus (T2DM) for further study. |
| format | Article |
| id | doaj-art-3a349b693e02430e8b5165f5a01aae9c |
| institution | Kabale University |
| issn | 2502-9258 2502-9266 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Komunitas Ilmuwan dan Profesional Muslim Indonesia |
| record_format | Article |
| series | Communications in Science and Technology |
| spelling | doaj-art-3a349b693e02430e8b5165f5a01aae9c2025-01-04T01:17:06ZengKomunitas Ilmuwan dan Profesional Muslim IndonesiaCommunications in Science and Technology2502-92582502-92662024-12-019232233010.21924/cst.9.2.2024.14971497Discovery of thymol-fused chalcones as new competitive \(\alpha\)-glucosidase inhibitors: Design, synthesis, biological evaluation, and molecular modeling studiesAde Danova0Elvira Hermawati1Warinthorn Chavasiri2Didin Mujahidin3Anita Alni4Robby Roswanda5Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha No.10, Bandung, West Java 40132, Indonesia.Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha No.10, Bandung, West Java 40132, Indonesia.Center of Excellence in Natural Products Chemistry, Department of Chemistry, Faculty of Science, Chulalongkorn University, Bangkok 10330, Thailand.Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha No.10, Bandung, West Java 40132, Indonesia.Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha No.10, Bandung, West Java 40132, Indonesia.Organic Chemistry Division, Department of Chemistry, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, Jl. Ganesha No.10, Bandung, West Java 40132, Indonesia.This study aims to synthesize and evaluate the inhibitory activity of thymol derivatives targeting ?-glucosidase using in vitro and in silico studies. Ten thymol derivatives (2-11) including five new thymol-fused chalcones (7-11) were successfully synthesized. Among them, four compounds (4, 8, 9, 11) showed the best inhibitory activity with IC50 values of 18.45, 13.75, 8.86, and 10.67µM compared with acarbose (IC50 = 832.82 µM), respectively. The kinetic study of three new thymol-fused chalcones (8, 9, 11) exhibited a competitive inhibition. Molecular docking demonstrated the predicted interactions between ligand (8, 9, 11) and ?-glucosidase, which are responsible for inhibiting the enzyme's catalytic abilities. Furthermore, molecular dynamics simulation of the enzyme-ligand 9 complex indicated that this complex was stable in aqueous condition. This research contributes significantly to the understanding of thymol-fused chalcones that may have therapeutic potential and their possible application in the treatment of type 2 diabetes mellitus (T2DM) for further study.https://cst.kipmi.or.id/journal/article/view/1497thymolchalconediabetes mellitusmolecular dockingmolecular dynamics\(\alpha\)-glucosidase |
| spellingShingle | Ade Danova Elvira Hermawati Warinthorn Chavasiri Didin Mujahidin Anita Alni Robby Roswanda Discovery of thymol-fused chalcones as new competitive \(\alpha\)-glucosidase inhibitors: Design, synthesis, biological evaluation, and molecular modeling studies Communications in Science and Technology thymol chalcone diabetes mellitus molecular docking molecular dynamics \(\alpha\)-glucosidase |
| title | Discovery of thymol-fused chalcones as new competitive \(\alpha\)-glucosidase inhibitors: Design, synthesis, biological evaluation, and molecular modeling studies |
| title_full | Discovery of thymol-fused chalcones as new competitive \(\alpha\)-glucosidase inhibitors: Design, synthesis, biological evaluation, and molecular modeling studies |
| title_fullStr | Discovery of thymol-fused chalcones as new competitive \(\alpha\)-glucosidase inhibitors: Design, synthesis, biological evaluation, and molecular modeling studies |
| title_full_unstemmed | Discovery of thymol-fused chalcones as new competitive \(\alpha\)-glucosidase inhibitors: Design, synthesis, biological evaluation, and molecular modeling studies |
| title_short | Discovery of thymol-fused chalcones as new competitive \(\alpha\)-glucosidase inhibitors: Design, synthesis, biological evaluation, and molecular modeling studies |
| title_sort | discovery of thymol fused chalcones as new competitive alpha glucosidase inhibitors design synthesis biological evaluation and molecular modeling studies |
| topic | thymol chalcone diabetes mellitus molecular docking molecular dynamics \(\alpha\)-glucosidase |
| url | https://cst.kipmi.or.id/journal/article/view/1497 |
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