Molecular Docking and 3-D QSAR Studies of Substituted 2,2-Bisaryl-Bicycloheptanes as Human 5-Lipoxygenase-Activating Protein (FLAP) Inhibitors
Leukotrienes have been shown to be involved in a variety of diseases such as cardiovascular diseases, cancer, asthma, ulcerative colitis, and rhinitis. 5-Lipoxygenase-Activating Protein (FLAP) was found to be a key enzyme of leukotriene synthesis. Comparative Molecular Field Analysis (CoMFA) and mol...
| Main Authors: | , , , , , |
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| Format: | Journal Article |
| Published: |
Wiley
2008
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| Online Access: | http://hdl.handle.net/20.500.11937/10087 |
| _version_ | 1848746133555249152 |
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| author | Ma, X. Zhou, L. Zuo, Zhili Liu, J. Yang, M. Wang, R. |
| author_facet | Ma, X. Zhou, L. Zuo, Zhili Liu, J. Yang, M. Wang, R. |
| author_sort | Ma, X. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Leukotrienes have been shown to be involved in a variety of diseases such as cardiovascular diseases, cancer, asthma, ulcerative colitis, and rhinitis. 5-Lipoxygenase-Activating Protein (FLAP) was found to be a key enzyme of leukotriene synthesis. Comparative Molecular Field Analysis (CoMFA) and molecular docking studies were carried out on a series of substituted 2,2-bisaryl-bicycloheptanes FLAP inhibitors. The docking results provided a reliable conformational alignment scheme for 3-D QSAR model. Based on the docking conformations, highly predictive CoMFA model was performed with a leave-one-out cross-validated q2 of 0.651. The noncross-validated analysis with four optimum components revealed a conventional r2 value of 0.972, F=175.674, and an estimated standard error of 0.169. The predictive ability of this model was validated by the testing set with a conventional r2 value of 0.920. The analyses may be used to design more potent FLAP inhibitors and predict their activities prior to synthesis. |
| first_indexed | 2025-11-14T06:28:25Z |
| format | Journal Article |
| id | curtin-20.500.11937-10087 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T06:28:25Z |
| publishDate | 2008 |
| publisher | Wiley |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-100872017-09-13T16:02:37Z Molecular Docking and 3-D QSAR Studies of Substituted 2,2-Bisaryl-Bicycloheptanes as Human 5-Lipoxygenase-Activating Protein (FLAP) Inhibitors Ma, X. Zhou, L. Zuo, Zhili Liu, J. Yang, M. Wang, R. Leukotrienes have been shown to be involved in a variety of diseases such as cardiovascular diseases, cancer, asthma, ulcerative colitis, and rhinitis. 5-Lipoxygenase-Activating Protein (FLAP) was found to be a key enzyme of leukotriene synthesis. Comparative Molecular Field Analysis (CoMFA) and molecular docking studies were carried out on a series of substituted 2,2-bisaryl-bicycloheptanes FLAP inhibitors. The docking results provided a reliable conformational alignment scheme for 3-D QSAR model. Based on the docking conformations, highly predictive CoMFA model was performed with a leave-one-out cross-validated q2 of 0.651. The noncross-validated analysis with four optimum components revealed a conventional r2 value of 0.972, F=175.674, and an estimated standard error of 0.169. The predictive ability of this model was validated by the testing set with a conventional r2 value of 0.920. The analyses may be used to design more potent FLAP inhibitors and predict their activities prior to synthesis. 2008 Journal Article http://hdl.handle.net/20.500.11937/10087 10.1002/qsar.200810053 Wiley restricted |
| spellingShingle | Ma, X. Zhou, L. Zuo, Zhili Liu, J. Yang, M. Wang, R. Molecular Docking and 3-D QSAR Studies of Substituted 2,2-Bisaryl-Bicycloheptanes as Human 5-Lipoxygenase-Activating Protein (FLAP) Inhibitors |
| title | Molecular Docking and 3-D QSAR Studies of Substituted 2,2-Bisaryl-Bicycloheptanes as Human 5-Lipoxygenase-Activating Protein (FLAP) Inhibitors |
| title_full | Molecular Docking and 3-D QSAR Studies of Substituted 2,2-Bisaryl-Bicycloheptanes as Human 5-Lipoxygenase-Activating Protein (FLAP) Inhibitors |
| title_fullStr | Molecular Docking and 3-D QSAR Studies of Substituted 2,2-Bisaryl-Bicycloheptanes as Human 5-Lipoxygenase-Activating Protein (FLAP) Inhibitors |
| title_full_unstemmed | Molecular Docking and 3-D QSAR Studies of Substituted 2,2-Bisaryl-Bicycloheptanes as Human 5-Lipoxygenase-Activating Protein (FLAP) Inhibitors |
| title_short | Molecular Docking and 3-D QSAR Studies of Substituted 2,2-Bisaryl-Bicycloheptanes as Human 5-Lipoxygenase-Activating Protein (FLAP) Inhibitors |
| title_sort | molecular docking and 3-d qsar studies of substituted 2,2-bisaryl-bicycloheptanes as human 5-lipoxygenase-activating protein (flap) inhibitors |
| url | http://hdl.handle.net/20.500.11937/10087 |