title: Cytotoxicity activity of L-proline analogues of anthraquinone-2-carboxylic acid in breast cancer MCF-7 cells.
abstract: Although prolidase [E.C.3.4.13.9] is found in normal cells, substantially increased levels are found in some neoplastic tissues. Prolidase evokes the ability to hydrolyse the imido-bond of various low molecular weight compounds coupled to L-proline. The synthesis of three proline analogues of anthraquinone-2-carboxylic acid (1-3) has been performed. Treatment of these prodrugs with prolidase generated L-proline and the free drug, demonstrating their substrate susceptibility prolidase. The concentrations of 1, 2 and 3 needed to inhibit [1H]thymidine incorporation into DNA by 50% (IC50) in breast cancer MCF-7 cells were found to be 185 +/- 5 microM, 107 +/- 6 microM and 87 +/- 6 microM, respectively, suggesting a lower cytotoxic potency of these compounds compared to Hoechst 33228 (IC50 = 55 +/- 6 microM).
authors.affiliation: Department of Medicinal Chemistry, Medical Academy, Białystok, Poland. kbiel@amb.ac.bialystok.pl
authors.forename: A
authors.initials: A
authors.lastname: Bielawska
authors.forename: K
authors.initials: K
authors.lastname: Bielawski
authors.forename: J
authors.initials: J
authors.lastname: Pałka
mesh_terms: D000880:Anthraquinones / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D001943:Breast Neoplasms; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D005260:Female; D006801:Humans; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology; D011392:Proline / Q000138:chemical synthesis / Q000494:pharmacology*; D013936:Thymidine / Q000493:pharmacokinetics; D014316:Tritium; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D011355:Prodrugs; D014316:Tritium; C085798:9,10-anthraquinone 2-carboxylic acid; D011392:Proline; D013936:Thymidine