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Int. J. Mol. Sci. 2011, 12(10), 7022-7037; doi:10.3390/ijms12107022
Article

Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) Studies on α1A-Adrenergic Receptor Antagonists Based on Pharmacophore Molecular Alignment

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1 Pharmaceutical Research Center, Guangzhou Medical College, Guangzhou, Guangdong 510182, China 2 Department of Food and Bioengineering, Guangdong Industry Technical College, Guangzhou, Guangdong 510300, China
* Author to whom correspondence should be addressed.
Received: 24 May 2011 / Revised: 5 September 2011 / Accepted: 11 October 2011 / Published: 20 October 2011

Abstract

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.
Keywords: CoMFA; CoMSIA; pharmacophore-based molecular alignment; α1A-adrenoceptor antagonists; GALAHAD; activity prediction CoMFA; CoMSIA; pharmacophore-based molecular alignment; α1A-adrenoceptor antagonists; GALAHAD; activity prediction
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Zhao, X.; Chen, M.; Huang, B.; Ji, H.; Yuan, M. Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) Studies on α1A-Adrenergic Receptor Antagonists Based on Pharmacophore Molecular Alignment. Int. J. Mol. Sci. 2011, 12, 7022-7037.

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