title: Reversed-phase liquid chromatography with octadecylsilyl, immobilized artificial membrane and cholesterol columns in correlation studies with in silico biological descriptors of newly synthesized antiproliferative and analgesic active compounds.
abstract: Reversed-phase liquid chromatography (RPLC) with different stationary phases, i.e., octadecylsilyl, immobilized artificial membrane and immobilized cholesterol, was used to study lipophilicity of 56 newly-designed 7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-ones and 2,6,7,8-tetrahydroimidazo[2,1-c][1,2,4]triazine-3,4-diones with potential anti-proliferative, anti-metastatic and analgesic activities. Extrapolated retention parameters that correspond to pure buffer as the mobile phase, i.e., logkw values are used as chromatographic lipophilicities. The lipophilic properties of compounds also are characterized by computed logP values and basic pharmacokinetic descriptors calculated in silico with the use of ACD/Percepta software according to Abraham's linear solvation energy relationship. Chromatographic and partitioning parameters are compared with biological descriptors using principal component analysis (PCA), and similarities and dissimilarities between variables and compounds are described. Highly significant, predictive relationships between biological descriptors and chromatographic parameters are obtained. Reversed parabolic relationships, which have very good statistical quality between various biological descriptors, i.e., logKsc, logKp, logBB, and logKhsa, and the logkw values, indicate the advantages of a cholesterol column in comparison with immobilized artificial membrane and octadecylsilyl stationary phase.
authors.affiliation: Maria Curie-Skłodowska University, Faculty of Chemistry, Department of Physical Chemistry, Maria Curie-Skłodowska Sq. 3, 20-031 Lublin, Poland. Electronic address: malgorzata.janicka@poczta.umcs.lublin.pl.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Janicka
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Sztanke
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Sztanke
mesh_terms: D000700:Analgesics / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification*; D002784:Cholesterol / Q000737:chemistry*; D056148:Chromatography, Reverse-Phase / Q000295:instrumentation / Q000379:methods*; D003198:Computer Simulation; D006131:Growth Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification*; D015394:Molecular Structure
chemical_list: D000700:Analgesics; D006131:Growth Inhibitors; D002784:Cholesterol
keywords: Biological descriptors; Cholesterol column; Lipophilicity; Principal component analysis; Reversed-phase liquid chromatography