title: Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) studies on α(1A)-adrenergic receptor antagonists based on pharmacophore molecular alignment.
abstract: The α(1A)-adrenergic receptor (α(1A)-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 α(1A)-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-oneout cross-validation correlation coefficients were q(2) (CoMFA) = 0.840 and q(2) (CoMSIA) = 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 (r(2) (pred) (/CoMFA) = 0.694; r(2) (pred) (/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 α(1A)-AR antagonists.
authors.affiliation: Pharmaceutical Research Center, Guangzhou Medical College, Guangzhou, Guangdong 510182, China; E-Mails:  zhaoxin.gy@gmail.com  (X.Z.);  gzminsheng@vip.163.com  (M.C.);  guangyihby@126.com  (B.H.);  dljih@126.com  (H.J.).
authors.forename: Xin
authors.initials: X
authors.lastname: Zhao
authors.forename: Minsheng
authors.initials: M
authors.lastname: Chen
authors.forename: Biyun
authors.initials: B
authors.lastname: Huang
authors.forename: Hong
authors.initials: H
authors.lastname: Ji
authors.forename: Mu
authors.initials: M
authors.lastname: Yuan
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D020134:Catalytic Domain; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D062105:Molecular Docking Simulation; D021281:Quantitative Structure-Activity Relationship; D018340:Receptors, Adrenergic, alpha-1 / Q000737:chemistry* / Q000378:metabolism; D055672:Static Electricity
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D018340:Receptors, Adrenergic, alpha-1
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