title: Statistical Analysis of the Impact of Molecular Descriptors on Cytotoxicity of Thiourea Derivatives Incorporating 2-Aminothiazole Scaffold.
abstract: Chemical reactivity descriptors and lipophilicyty (log P) were evaluated via semi-empirical method for the quantum calculation of molecular electronic structure (PM3) in order to clarify the structure-cytotoxic activity relationships of disubstutited thioureas. Analysed compounds were obtained by the linkage of 2-aminothiazole ring, thiourea and substituted phenyl ring. The detailed examination was carried out to establish correlation between descriptors and cytotoxic activity against the MT-4 cells for 11 compounds. For the most active compounds (6 compounds) cytotoxic activity against three cancer cell lines (CCRF-CEM, WIL-2NS, CCRF-SB) and normal human cell (HaCaT) was determined. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and lactate dehydrogenase (LDH) release were assessed. Regression analysis revealed that electrophilicity index and chemical potential significantly contributed to expain the thioureas cytotoxic potential.
authors.affiliation: Faculty of Automatic Control, Electronics and Computer Science, Silesian University of Technology.
authors.forename: Anna
authors.initials: A
authors.lastname: Filipowska
authors.forename: Wojciech
authors.initials: W
authors.lastname: Filipowski
authors.forename: Ewaryst
authors.initials: E
authors.lastname: Tkacz
authors.forename: Grażyna
authors.initials: G
authors.lastname: Nowicka
authors.forename: Marta
authors.initials: M
authors.lastname: Struga
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000037:antagonists & inhibitors / Q000378:metabolism; D015233:Models, Statistical; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D013844:Thiazoles; C004483:2-aminothiazole; D007770:L-Lactate Dehydrogenase; D013890:Thiourea