title: Relationship between lipophilicity and antitumor activity of molecule library of Mannich ketones determined by high-performance liquid chromatography, clogP calculation and cytotoxicity test.
abstract: A series of Mannich ketones were synthesized in order to study the relative importance of structure and specific substitutions in relation to their lipophilicity and antitumor activity. Substitutions were carried out with morpholinyl, pirrolidinyl, piperidyl and tetrahydro-isoquinolyl groups in various positions on three different skeletons. Lipophilicity of Mannich ketones was characterised by chromatography data (log k') and by software calculated parameters (clogP). Compounds were tested on their ability to inhibit the proliferation of the A431 human adenocarcinoma cell line evaluated by MTT and apoptosis assays. The results suggest that the higher the lipophilicity values (log k' and clogP), the higher the antitumor and apoptotic activity of Mannich ketones. Determination of lipophilicity by measuring the log k' or by calculating the clogP values of the compounds may help to predict their biological activities.
authors.affiliation: Peptide Biochemistry Research Group of the Hungarian Academy of Sciences in Semmelweis University, Department of Medical Chemistry, Molecular Biology and Pathobiochemistry, Puskin, Budapest. fhollosy@puskin.sote.hu
authors.forename: Ferenc
authors.initials: F
authors.lastname: Hollósy
authors.forename: Tamás
authors.initials: T
authors.lastname: Lóránd
authors.forename: László
authors.initials: L
authors.lastname: Orfi
authors.forename: Dániel
authors.initials: D
authors.lastname: Erös
authors.forename: György
authors.initials: G
authors.lastname: Kéri
authors.forename: Miklós
authors.initials: M
authors.lastname: Idei
mesh_terms: D000970:Antineoplastic Agents / Q000378:metabolism* / Q000494:pharmacology*; D017209:Apoptosis; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007659:Ketones / Q000378:metabolism* / Q000494:pharmacology*; D050356:Lipid Metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D007659:Ketones