Synthesis of Anti-Inflammatory Drugs’ Chalcone Derivatives and a Study of Their Conformational Properties Through a Combination of Nuclear Magnetic Resonance Spectroscopy and Molecular Modeling
Background: In this study, two chalcone analogs were synthesized through in silico and experimental methods, and their potential to inhibit the lipoxygenase enzyme, which plays a role in the inflammation pathway, was assessed. Specifically, this study is a continuation of previous research in which...
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2025-01-01
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| author | Nikitas Georgiou Andromachi Tzani Kyriaki Vavougyiou Christos Papadopoulos Nikolaos Eleftheriadis Primož Šket Demeter Tzeli Tuomas Niemi-Aro Anastasia Detsi Thomas Mavromoustakos |
| author_facet | Nikitas Georgiou Andromachi Tzani Kyriaki Vavougyiou Christos Papadopoulos Nikolaos Eleftheriadis Primož Šket Demeter Tzeli Tuomas Niemi-Aro Anastasia Detsi Thomas Mavromoustakos |
| author_sort | Nikitas Georgiou |
| collection | DOAJ |
| description | Background: In this study, two chalcone analogs were synthesized through in silico and experimental methods, and their potential to inhibit the lipoxygenase enzyme, which plays a role in the inflammation pathway, was assessed. Specifically, this study is a continuation of previous research in which chalcone derivatives were synthesized and characterized. Objectives/Methods: In the current work, we present the re-synthesis of two chalcones, with a focus on their docking studies, NMR analysis, and dynamic simulations. The structure of each chalcone was elucidated through a combination of Nuclear Magnetic Resonance (NMR) and Density Functional Theory (DFT). The substituent effect on the absorption spectrum of the two chalcone derivatives was studied. Results: A “LOX–chalcone” complex, predicted by docking studies, was further examined using molecular dynamics (MD) simulations to evaluate the stability of the complex. After fully characterizing the “LOX–chalcone” complexes in silico, the atomic details of each chalcone’s interaction with LOX-1 and 5-LOX were revealed through Saturation Transfer Difference (STD) NMR (Nuclear Magnetic Resonance). Finally, their selectivity profile was investigated against human 15-LOX-1 and general Lipoxidase activity. Conclusions: The in silico methods suggest that chalcones could be promising lead compounds for drug designs targeting the LOX enzyme. |
| format | Article |
| id | doaj-art-2b6cddd4f196458e861101863d231381 |
| institution | Kabale University |
| issn | 1424-8247 |
| language | English |
| publishDate | 2025-01-01 |
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| series | Pharmaceuticals |
| spelling | doaj-art-2b6cddd4f196458e861101863d2313812025-01-24T13:45:21ZengMDPI AGPharmaceuticals1424-82472025-01-011818810.3390/ph18010088Synthesis of Anti-Inflammatory Drugs’ Chalcone Derivatives and a Study of Their Conformational Properties Through a Combination of Nuclear Magnetic Resonance Spectroscopy and Molecular ModelingNikitas Georgiou0Andromachi Tzani1Kyriaki Vavougyiou2Christos Papadopoulos3Nikolaos Eleftheriadis4Primož Šket5Demeter Tzeli6Tuomas Niemi-Aro7Anastasia Detsi8Thomas Mavromoustakos9Laboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, GreeceLaboratory of Organic Chemistry, Department of Chemical Sciences, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, 15780 Athens, GreeceLaboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, GreeceDepartment of Chemistry, University of Crete, Voutes, 70013 Heraklion, GreeceDepartment of Chemistry, University of Crete, Voutes, 70013 Heraklion, GreeceSlovenian NMR Centre, National Institute of Chemistry, SI-1001 Ljubljana, SloveniaLaboratory of Physical Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, GreeceInstitute of Biotechnology, Helsinki Institute of Life Sciences, Viikinkaari 1, P.O. Box 65, University of Helsinki, 00014 Helsinki, FinlandLaboratory of Organic Chemistry, Department of Chemical Sciences, School of Chemical Engineering, National Technical University of Athens, Heroon Polytechniou 9, Zografou Campus, 15780 Athens, GreeceLaboratory of Organic Chemistry, Department of Chemistry, National and Kapodistrian University of Athens, Panepistimioupolis Zografou, 11571 Athens, GreeceBackground: In this study, two chalcone analogs were synthesized through in silico and experimental methods, and their potential to inhibit the lipoxygenase enzyme, which plays a role in the inflammation pathway, was assessed. Specifically, this study is a continuation of previous research in which chalcone derivatives were synthesized and characterized. Objectives/Methods: In the current work, we present the re-synthesis of two chalcones, with a focus on their docking studies, NMR analysis, and dynamic simulations. The structure of each chalcone was elucidated through a combination of Nuclear Magnetic Resonance (NMR) and Density Functional Theory (DFT). The substituent effect on the absorption spectrum of the two chalcone derivatives was studied. Results: A “LOX–chalcone” complex, predicted by docking studies, was further examined using molecular dynamics (MD) simulations to evaluate the stability of the complex. After fully characterizing the “LOX–chalcone” complexes in silico, the atomic details of each chalcone’s interaction with LOX-1 and 5-LOX were revealed through Saturation Transfer Difference (STD) NMR (Nuclear Magnetic Resonance). Finally, their selectivity profile was investigated against human 15-LOX-1 and general Lipoxidase activity. Conclusions: The in silico methods suggest that chalcones could be promising lead compounds for drug designs targeting the LOX enzyme.https://www.mdpi.com/1424-8247/18/1/88chalconesinflammationLOXNMRmolecular dynamics |
| spellingShingle | Nikitas Georgiou Andromachi Tzani Kyriaki Vavougyiou Christos Papadopoulos Nikolaos Eleftheriadis Primož Šket Demeter Tzeli Tuomas Niemi-Aro Anastasia Detsi Thomas Mavromoustakos Synthesis of Anti-Inflammatory Drugs’ Chalcone Derivatives and a Study of Their Conformational Properties Through a Combination of Nuclear Magnetic Resonance Spectroscopy and Molecular Modeling Pharmaceuticals chalcones inflammation LOX NMR molecular dynamics |
| title | Synthesis of Anti-Inflammatory Drugs’ Chalcone Derivatives and a Study of Their Conformational Properties Through a Combination of Nuclear Magnetic Resonance Spectroscopy and Molecular Modeling |
| title_full | Synthesis of Anti-Inflammatory Drugs’ Chalcone Derivatives and a Study of Their Conformational Properties Through a Combination of Nuclear Magnetic Resonance Spectroscopy and Molecular Modeling |
| title_fullStr | Synthesis of Anti-Inflammatory Drugs’ Chalcone Derivatives and a Study of Their Conformational Properties Through a Combination of Nuclear Magnetic Resonance Spectroscopy and Molecular Modeling |
| title_full_unstemmed | Synthesis of Anti-Inflammatory Drugs’ Chalcone Derivatives and a Study of Their Conformational Properties Through a Combination of Nuclear Magnetic Resonance Spectroscopy and Molecular Modeling |
| title_short | Synthesis of Anti-Inflammatory Drugs’ Chalcone Derivatives and a Study of Their Conformational Properties Through a Combination of Nuclear Magnetic Resonance Spectroscopy and Molecular Modeling |
| title_sort | synthesis of anti inflammatory drugs chalcone derivatives and a study of their conformational properties through a combination of nuclear magnetic resonance spectroscopy and molecular modeling |
| topic | chalcones inflammation LOX NMR molecular dynamics |
| url | https://www.mdpi.com/1424-8247/18/1/88 |
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