title: Evaluation of electronic, lipophilic and membrane affinity effects on antiproliferative activity of 5-substituted-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles against various human cancer cells.
abstract: The QSAR studies of 5-substituted-2-(2,4-dihydroxyphenyl)-1,3,4-thiadiazoles set of antiproliferative activity against human cancer cell lines have been performed. Electronic properties of compounds were estimated by the Hartree-Fock method at 6-31G** level. Lipophilicity and membrane affinity parameters were determined by the chromatographic methods RP-8 OPLC and IAM HPLC, respectively. Mono- and multivariable regression analyses were performed. The principle factor for determination of activity of compounds is partial charge of nitrogen (q(N3), q(N4)) and carbon (q(C5)) atoms of the 1,3,4-thiadiazole ring. Biological effect is also connected with molar refractivity (CMR) and lipophilicity of derivatives obtained by RP-8 chromatography. The analysis of the QSAR equations for individual cell lines indicates both similarities and differences of electron, steric factors and hydrophobic-hydrophilic character of the analogues of the tested set affecting the antiproliferative activity.
authors.affiliation: Department of Chemistry, Agricultural University, Akademicka 15, 20-950 Lublin, Poland. joanna.matysiak@ar.lublin.pl
authors.forename: Joanna
authors.initials: J
authors.lastname: Matysiak
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D021281:Quantitative Structure-Activity Relationship; D013830:Thiadiazoles / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D013830:Thiadiazoles