title: L-proline analogues of anthraquinone-2-carboxylic acid: cytotoxic activity in breast cancer MCF-7 cells and inhibitory activity against topoisomerase I and II.
abstract: A series of proline analogues of anthraquinone-2-carboxylic acid (1-3) were synthesized and evaluated for cytotoxic activity in the cultured breast cancer MCF-7 cells. The concentrations of 1, 2 and 3 needed to inhibit [3H]thymidine incorporation into DNA by 50% (IC50) were found to be 107 +/- 6 microM, 185 +/- 5 microM and 87 +/- 6 microM, respectively. To test whether cytotoxic properties were related to topoisomerase action, the most potent compounds 1 and 3 were evaluated in a cell-free system. Compound 3, which contains a basic substituent at C terminus of the amino acid such as (dimethylamino)propyl inhibited the catalytic activity of both topoisomerases I and II at a concentration of 30 and 60 microM, respectively. However, compound 1 containing an electrostatically neutral moiety, such as methyl ester did not inhibit topoisomerase I or topoisomerase II. In summary, compound 3 is a promising lead compound for a further structural variation in the design of new antitumour drugs.
authors.affiliation: Department of Medicinal Chemistry and Drug Technology, Medical Academy of Białystok, Poland. kbiel@amb.ac.bialystok.pl
authors.forename: A
authors.initials: A
authors.lastname: Bielawska
authors.forename: K
authors.initials: K
authors.lastname: Kosk
authors.forename: K
authors.initials: K
authors.lastname: Bielawski
mesh_terms: D000880:Anthraquinones / Q000138:chemical synthesis / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D006690:Bisbenzimidazole / Q000494:pharmacology; D001943:Breast Neoplasms; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D005260:Female; D005456:Fluorescent Dyes / Q000494:pharmacology; D006801:Humans; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D000880:Anthraquinones; D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D004791:Enzyme Inhibitors; D005456:Fluorescent Dyes; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; C085798:9,10-anthraquinone 2-carboxylic acid; D004247:DNA; D011392:Proline; D006690:Bisbenzimidazole; D013936:Thymidine