Next Article in Journal
Previous Article in Journal
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

1,2
, 1
, 1
, 1
 and 1,*
Received: 24 May 2011; in revised form: 5 September 2011 / Accepted: 11 October 2011 / Published: 20 October 2011
View Full-Text   |   Download PDF [814 KB, uploaded 19 June 2014]
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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Export to BibTeX |
EndNote


MDPI and ACS Style

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.

AMA Style

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. International Journal of Molecular Sciences. 2011; 12(10):7022-7037.

Chicago/Turabian Style

Zhao, Xin; Chen, Minsheng; Huang, Biyun; Ji, Hong; Yuan, Mu. 2011. "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. 12, no. 10: 7022-7037.


Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert