Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) Studies on α1A-Adrenergic Receptor Antagonists Based on Pharmacophore Molecular Alignment
The α1A-adrenergic receptor (α1A-AR) antagonist is useful in treating benign prostatic hyperplasia, lower urinary tract symptoms, and cardiac arrhythmia. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on a set of α1A-AR antagonists of N-aryl and N-nit...
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| Format: | Article |
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MDPI AG
2011-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | http://www.mdpi.com/1422-0067/12/10/7022/ |
| _version_ | 1811266282577723392 |
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| author | Mu Yuan Minsheng Chen Biyun Huang Xin Zhao Hong Ji |
| author_facet | Mu Yuan Minsheng Chen Biyun Huang Xin Zhao Hong Ji |
| author_sort | Mu Yuan |
| collection | DOAJ |
| description | The α1A-adrenergic receptor (α1A-AR) antagonist is useful in treating benign prostatic hyperplasia, lower urinary tract symptoms, and cardiac arrhythmia. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on a set of α1A-AR antagonists of N-aryl and N-nitrogen class. Statistically significant models constructed from comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were established based on a training set of 32 ligands using pharmacophore-based molecular alignment. The leave-one-out cross-validation correlation coefficients were q2CoMFA = 0.840 and q2CoMSIA = 0.840. The high correlation between the cross-validated/predicted and experimental activities of a test set of 12 ligands revealed that the CoMFA and CoMSIA models were robust (r2pred/CoMFA = 0.694; r2pred/CoMSIA = 0.671). The generated models suggested that electrostatic, hydrophobic, and hydrogen bonding interactions play important roles between ligands and receptors in the active site. Our study serves as a guide for further experimental investigations on the synthesis of new compounds. Structural modifications based on the present 3D-QSAR results may lead to the discovery of other α1A-AR antagonists. |
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| institution | Directory Open Access Journal |
| issn | 1422-0067 |
| language | English |
| last_indexed | 2024-04-12T20:39:22Z |
| publishDate | 2011-10-01 |
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| spelling | doaj.art-6afaa941b9c4405180ab352d932d5c532022-12-22T03:17:27ZengMDPI AGInternational Journal of Molecular Sciences1422-00672011-10-0112107022703710.3390/ijms12107022Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) Studies on α1A-Adrenergic Receptor Antagonists Based on Pharmacophore Molecular AlignmentMu YuanMinsheng ChenBiyun HuangXin ZhaoHong JiThe α1A-adrenergic receptor (α1A-AR) antagonist is useful in treating benign prostatic hyperplasia, lower urinary tract symptoms, and cardiac arrhythmia. Three-dimensional quantitative structure-activity relationship (3D-QSAR) studies were performed on a set of α1A-AR antagonists of N-aryl and N-nitrogen class. Statistically significant models constructed from comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were established based on a training set of 32 ligands using pharmacophore-based molecular alignment. The leave-one-out cross-validation correlation coefficients were q2CoMFA = 0.840 and q2CoMSIA = 0.840. The high correlation between the cross-validated/predicted and experimental activities of a test set of 12 ligands revealed that the CoMFA and CoMSIA models were robust (r2pred/CoMFA = 0.694; r2pred/CoMSIA = 0.671). The generated models suggested that electrostatic, hydrophobic, and hydrogen bonding interactions play important roles between ligands and receptors in the active site. Our study serves as a guide for further experimental investigations on the synthesis of new compounds. Structural modifications based on the present 3D-QSAR results may lead to the discovery of other α1A-AR antagonists.http://www.mdpi.com/1422-0067/12/10/7022/CoMFACoMSIApharmacophore-based molecular alignmentα1A-adrenoceptor antagonistsGALAHADactivity prediction |
| spellingShingle | Mu Yuan Minsheng Chen Biyun Huang Xin Zhao Hong Ji Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) Studies on α1A-Adrenergic Receptor Antagonists Based on Pharmacophore Molecular Alignment International Journal of Molecular Sciences CoMFA CoMSIA pharmacophore-based molecular alignment α1A-adrenoceptor antagonists GALAHAD activity prediction |
| title | Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) Studies on α1A-Adrenergic Receptor Antagonists Based on Pharmacophore Molecular Alignment |
| title_full | Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) Studies on α1A-Adrenergic Receptor Antagonists Based on Pharmacophore Molecular Alignment |
| title_fullStr | Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) Studies on α1A-Adrenergic Receptor Antagonists Based on Pharmacophore Molecular Alignment |
| title_full_unstemmed | Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) Studies on α1A-Adrenergic Receptor Antagonists Based on Pharmacophore Molecular Alignment |
| title_short | Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) Studies on α1A-Adrenergic Receptor Antagonists Based on Pharmacophore Molecular Alignment |
| title_sort | comparative molecular field analysis comfa and comparative molecular similarity indices analysis comsia studies on α1a adrenergic receptor antagonists based on pharmacophore molecular alignment |
| topic | CoMFA CoMSIA pharmacophore-based molecular alignment α1A-adrenoceptor antagonists GALAHAD activity prediction |
| url | http://www.mdpi.com/1422-0067/12/10/7022/ |
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