title: Comparative molecular field analysis of chromatographic hydrophobicity indices for some coumarin analogs.
abstract: The chromatographic hydrophobicity index (CHI) is an HPLC-based parameter that provides reliable guidance in optimization of pharmacological efficiency and adsorption, distribution, metabolism and exertion (ADME) profile of drug candidates. In the present work, classical and three-dimensional quantitative structure-property relationship (QSPR) models were developed for prediction of CHI values of some 4-hydroxycoumarin analogs on immobilized artificial membrane column. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) as 3D-QSPR methods were performed to gain insight into the key structural factors affecting on the chromatographic hydrophobicity of interested chemicals. The calculated parameters of Q2, R2and standard error were 0.545, 0.996 and 0.773 for CoMFA model and 0.815, 0.986 and 1.44 for CoMSIA model, respectively. The contour maps for steric fields of the CoMFA model illustrate that the hydrophobicity of chemicals will be higher when the positions of R6, R7 and R8 in the 4-hydroxycuomarin ring are substituted by alkyl groups. Moreover, by the analysis of the plots of electrostatic fields, it was concluded that the CHI value greatly increases if one hydrogen on coumarin ring is substituted by the F, Cl, Br, OH or OCH3group.
authors: Laboratory of Chemometrics, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran.
authors: Mohammad Hossein
authors: MH
authors: Fatemi
authors: Laboratory of Chemometrics, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran.
authors: Zahra
authors: Z
authors: Shakoori
authors: Laboratory of Chemometrics, Faculty of Chemistry, University of Mazandaran, Babolsar, Iran.
authors: Kobra
authors: K
authors: Samghani
mesh_terms: D015110:4-Hydroxycoumarins / Q000737:chemistry* / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D021281:Quantitative Structure-Activity Relationship; D060388:Support Vector Machine
chemical_list: D015110:4-Hydroxycoumarins; D003374:Coumarins
keywords: chromatographic hydrophobicity index; comparative molecular field analysis; comparative molecular similarity indices analysis; quantitative structure property relationship