title: CP-MLR/PLS directed QSAR study on apical sodium-codependent bile acid transporter inhibition activity of benzothiepines.
abstract: The apical sodium-codependent bile acid transporter (ASBT) inhibition activity of benzothiepine derivatives have been analyzed based on topological and molecular features. Analysis of the structural features in conjunction with the biological endpoints in Combinatorial Protocol in Multiple Linear Regression (CP-MLR) led to the identification of 21 descriptors for modeling the activity. The study clearly suggested that the role of Randic shape index (path/walk ratio 3) and topological charges of 2-, 5-, and 6-orders to optimize the ASBT inhibitory activity of titled compounds. The influence of atomic van der Waals volumes, masses, Sanderson electronegativities, and polarizabilities are indicated via different lags of Moran and Geary autocorrelations. Presence of tertiary aromatic amine functionality in molecular structure has also shown its relevance in rationalizing the biological actions of benzothiepines. The PLS analysis has confirmed the dominance of information content of CP-MLR identified descriptors for modeling the activity when compared to those of the leftover ones.
authors.affiliation: Department of Chemistry, S. K. Government College, Sikar, 332001, India. bksharma_sikar@rediffmail.com
authors.forename: Brij Kishore
authors.initials: BK
authors.lastname: Sharma
authors.forename: Prithvi
authors.initials: P
authors.lastname: Singh
authors.forename: Pradeep
authors.initials: P
authors.lastname: Pilania
authors.forename: Kirti
authors.initials: K
authors.lastname: Sarbhai
authors.forename: Yenamandra S
authors.initials: YS
authors.lastname: Prabhakar
mesh_terms: D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D003497:Cyclic N-Oxides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016014:Linear Models; D029363:Organic Anion Transporters, Sodium-Dependent / Q000037:antagonists & inhibitors*; D021281:Quantitative Structure-Activity Relationship; D027981:Symporters / Q000037:antagonists & inhibitors*
chemical_list: D003497:Cyclic N-Oxides; D029363:Organic Anion Transporters, Sodium-Dependent; D027981:Symporters; C071908:sodium-bile acid cotransporter