Lipoxygenase Inhibition Activity of Coumarin Derivatives—QSAR and Molecular Docking Study
Lipoxygenases (LOXs) are a family of enzymes found in plants, mammals, and microorganisms. In animals and plants, the enzyme has the capability for the peroxidation of unsaturated fatty acids. Although LOXs participate in the plant defense system, the enzyme’s metabolites can have numerous negative...
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MDPI AG
2020-07-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/13/7/154 |
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| author | Melita Lončarić Ivica Strelec Valentina Pavić Domagoj Šubarić Vesna Rastija Maja Molnar |
| author_facet | Melita Lončarić Ivica Strelec Valentina Pavić Domagoj Šubarić Vesna Rastija Maja Molnar |
| author_sort | Melita Lončarić |
| collection | DOAJ |
| description | Lipoxygenases (LOXs) are a family of enzymes found in plants, mammals, and microorganisms. In animals and plants, the enzyme has the capability for the peroxidation of unsaturated fatty acids. Although LOXs participate in the plant defense system, the enzyme’s metabolites can have numerous negative effects on human health. Therefore, many types of research are searching for compounds that can inhibit LOXs. The best quantitative structure–activity relationship (QSAR) model was obtained using a Genetic Algorithm (GA). Molecular docking was performed with iGEMDOCK. The inhibition of lipoxygenase was in the range of 7.1 to 96.6%, and the inhibition of lipid peroxidation was 7.0–91.0%. Among the synthesized compounds, the strongest inhibitor of soybean LOX-3 (96.6%) was found to be 3-benzoyl-7-(benzyloxy)-2<i>H</i>-chromen-2-one. A lipid peroxidation inhibition of 91.0% was achieved with ethyl 7-methoxy-2-oxo-2<i>H</i>-chromene-3-carboxylate. The docking scores for the soybean LOX-3 and human 5-LOX also indicated that this compound has the best affinity for these LOX enzymes. The best multiple linear QSAR model contains the atom-centered fragment descriptors <i>C-06</i>, <i>RDF035p</i>, and <i>HATS8p</i>. QSAR and molecular docking studies elucidated the structural features important for the enhanced inhibitory activity of the most active compounds, such as the presence of the benzoyl ring at the 3-position of coumarin’s core. Compounds with benzoyl substituents are promising candidates as potent lipoxygenase inhibitors. |
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| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-10T18:23:59Z |
| publishDate | 2020-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-b14dabbb1f45424d84082130175d0ecd2023-11-20T07:09:00ZengMDPI AGPharmaceuticals1424-82472020-07-0113715410.3390/ph13070154Lipoxygenase Inhibition Activity of Coumarin Derivatives—QSAR and Molecular Docking StudyMelita Lončarić0Ivica Strelec1Valentina Pavić2Domagoj Šubarić3Vesna Rastija4Maja Molnar5Faculty of Food Faculty Osijek, Josip Juraj Strossmayer University, 31000 Osijek, CroatiaFaculty of Food Faculty Osijek, Josip Juraj Strossmayer University, 31000 Osijek, CroatiaDepartment of Biology, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, CroatiaDepartment of Agroecology and Environmental Protection, Faculty of Agrobiotechnical Sciences Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, CroatiaDepartment of Agroecology and Environmental Protection, Faculty of Agrobiotechnical Sciences Osijek, Josip Juraj Strossmayer University of Osijek, 31000 Osijek, CroatiaFaculty of Food Faculty Osijek, Josip Juraj Strossmayer University, 31000 Osijek, CroatiaLipoxygenases (LOXs) are a family of enzymes found in plants, mammals, and microorganisms. In animals and plants, the enzyme has the capability for the peroxidation of unsaturated fatty acids. Although LOXs participate in the plant defense system, the enzyme’s metabolites can have numerous negative effects on human health. Therefore, many types of research are searching for compounds that can inhibit LOXs. The best quantitative structure–activity relationship (QSAR) model was obtained using a Genetic Algorithm (GA). Molecular docking was performed with iGEMDOCK. The inhibition of lipoxygenase was in the range of 7.1 to 96.6%, and the inhibition of lipid peroxidation was 7.0–91.0%. Among the synthesized compounds, the strongest inhibitor of soybean LOX-3 (96.6%) was found to be 3-benzoyl-7-(benzyloxy)-2<i>H</i>-chromen-2-one. A lipid peroxidation inhibition of 91.0% was achieved with ethyl 7-methoxy-2-oxo-2<i>H</i>-chromene-3-carboxylate. The docking scores for the soybean LOX-3 and human 5-LOX also indicated that this compound has the best affinity for these LOX enzymes. The best multiple linear QSAR model contains the atom-centered fragment descriptors <i>C-06</i>, <i>RDF035p</i>, and <i>HATS8p</i>. QSAR and molecular docking studies elucidated the structural features important for the enhanced inhibitory activity of the most active compounds, such as the presence of the benzoyl ring at the 3-position of coumarin’s core. Compounds with benzoyl substituents are promising candidates as potent lipoxygenase inhibitors.https://www.mdpi.com/1424-8247/13/7/154lipoxygenasecoumarinslipid peroxidationantioxidant activityQSARmolecular docking |
| spellingShingle | Melita Lončarić Ivica Strelec Valentina Pavić Domagoj Šubarić Vesna Rastija Maja Molnar Lipoxygenase Inhibition Activity of Coumarin Derivatives—QSAR and Molecular Docking Study Pharmaceuticals lipoxygenase coumarins lipid peroxidation antioxidant activity QSAR molecular docking |
| title | Lipoxygenase Inhibition Activity of Coumarin Derivatives—QSAR and Molecular Docking Study |
| title_full | Lipoxygenase Inhibition Activity of Coumarin Derivatives—QSAR and Molecular Docking Study |
| title_fullStr | Lipoxygenase Inhibition Activity of Coumarin Derivatives—QSAR and Molecular Docking Study |
| title_full_unstemmed | Lipoxygenase Inhibition Activity of Coumarin Derivatives—QSAR and Molecular Docking Study |
| title_short | Lipoxygenase Inhibition Activity of Coumarin Derivatives—QSAR and Molecular Docking Study |
| title_sort | lipoxygenase inhibition activity of coumarin derivatives qsar and molecular docking study |
| topic | lipoxygenase coumarins lipid peroxidation antioxidant activity QSAR molecular docking |
| url | https://www.mdpi.com/1424-8247/13/7/154 |
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