Relationship between lipophilicity and antitumor activity of molecule library of Mannich ketones determined by high-performance liquid chromatography, clogP calculation and cytotoxicity test.
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.
Hollósy
Ferenc
F
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
Lóránd
Tamás
T
Orfi
László
L
Erös
Dániel
D
Kéri
György
G
Idei
Miklós
M
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
D000970:Antineoplastic Agents; D007659:Ketones