QSAR modeling of benzoquinone derivatives as 5-lipoxygenase inhibitors
The inhibitors of 5-LOX control the overproduction of pro-inflammatory mediators known as leukotrienes (LTs) and thus have therapeutic relevance in the treatment of various diseases like asthma, rheumatoid arthritis, inflammatory bowel disease and certain types of cancers. This has increased the sea...
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| Format: | Article |
| Language: | English |
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Tsinghua University Press
2019-03-01
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| Series: | Food Science and Human Wellness |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2213453018301241 |
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| author | T.K. Shameera Ahamed Vijisha K. Rajan K. Muraleedharan |
| author_facet | T.K. Shameera Ahamed Vijisha K. Rajan K. Muraleedharan |
| author_sort | T.K. Shameera Ahamed |
| collection | DOAJ |
| description | The inhibitors of 5-LOX control the overproduction of pro-inflammatory mediators known as leukotrienes (LTs) and thus have therapeutic relevance in the treatment of various diseases like asthma, rheumatoid arthritis, inflammatory bowel disease and certain types of cancers. This has increased the search for efficient therapeutic agents for protein 5-LOX and this process is now primarily based on QSAR. In this study, we have developed four different quantitative structure and 5-LOX inhibition activity relationship models of benzoquinone derivative by exploiting CoMFA, RF, SVM, and MLR chemometric methods. Performance of the QSAR models was measured by using cross-validation technique as well as through the external test set prediction. RF model outperforms all other models. SVM and MLR models failed due to the poor performance of the external test set prediction. CoMFA model, which shows relatively good performance was used to explore the essential structural regions where the modification was necessary to design a novel scaffold with improved activity. Moreover, molecular docking of all the derivatives to the binding site of 5-LOX was done to show their binding mode and to identify critical interacting residues inside the active site of 5-LOX. The docking result confirms the stability and rationality of the CoMFA model. Keywords: 5-lipoxygenase, Benzoquinone, 2D-QSAR, 3D-QSAR, Molecular docking |
| format | Article |
| id | doaj-art-2d10d92f890e41db902b5201160fef32 |
| institution | Kabale University |
| issn | 2213-4530 |
| language | English |
| publishDate | 2019-03-01 |
| publisher | Tsinghua University Press |
| record_format | Article |
| series | Food Science and Human Wellness |
| spelling | doaj-art-2d10d92f890e41db902b5201160fef322025-02-03T02:38:53ZengTsinghua University PressFood Science and Human Wellness2213-45302019-03-01815362QSAR modeling of benzoquinone derivatives as 5-lipoxygenase inhibitorsT.K. Shameera Ahamed0Vijisha K. Rajan1K. Muraleedharan2Department of Chemistry, University of Calicut, Malappuram 673635, IndiaDepartment of Chemistry, University of Calicut, Malappuram 673635, IndiaCorresponding author.; Department of Chemistry, University of Calicut, Malappuram 673635, IndiaThe inhibitors of 5-LOX control the overproduction of pro-inflammatory mediators known as leukotrienes (LTs) and thus have therapeutic relevance in the treatment of various diseases like asthma, rheumatoid arthritis, inflammatory bowel disease and certain types of cancers. This has increased the search for efficient therapeutic agents for protein 5-LOX and this process is now primarily based on QSAR. In this study, we have developed four different quantitative structure and 5-LOX inhibition activity relationship models of benzoquinone derivative by exploiting CoMFA, RF, SVM, and MLR chemometric methods. Performance of the QSAR models was measured by using cross-validation technique as well as through the external test set prediction. RF model outperforms all other models. SVM and MLR models failed due to the poor performance of the external test set prediction. CoMFA model, which shows relatively good performance was used to explore the essential structural regions where the modification was necessary to design a novel scaffold with improved activity. Moreover, molecular docking of all the derivatives to the binding site of 5-LOX was done to show their binding mode and to identify critical interacting residues inside the active site of 5-LOX. The docking result confirms the stability and rationality of the CoMFA model. Keywords: 5-lipoxygenase, Benzoquinone, 2D-QSAR, 3D-QSAR, Molecular dockinghttp://www.sciencedirect.com/science/article/pii/S2213453018301241 |
| spellingShingle | T.K. Shameera Ahamed Vijisha K. Rajan K. Muraleedharan QSAR modeling of benzoquinone derivatives as 5-lipoxygenase inhibitors Food Science and Human Wellness |
| title | QSAR modeling of benzoquinone derivatives as 5-lipoxygenase inhibitors |
| title_full | QSAR modeling of benzoquinone derivatives as 5-lipoxygenase inhibitors |
| title_fullStr | QSAR modeling of benzoquinone derivatives as 5-lipoxygenase inhibitors |
| title_full_unstemmed | QSAR modeling of benzoquinone derivatives as 5-lipoxygenase inhibitors |
| title_short | QSAR modeling of benzoquinone derivatives as 5-lipoxygenase inhibitors |
| title_sort | qsar modeling of benzoquinone derivatives as 5 lipoxygenase inhibitors |
| url | http://www.sciencedirect.com/science/article/pii/S2213453018301241 |
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