Antiproliferative activity in vitro of new malatoplatinum(ll) complexes.
The results of studies on antiproliferative activity in vitro of nine new platinum(II) complexes against cells of eight human and six murine neoplastic cell lines are described. New complexes with the anionic rest originating from enantiomeric forms of hydroxydicarboxylic malic acid were synthesized to obtain agents with increased water solubility and decreased toxicity. Three compounds, coded 1-3, with ethylenediamine as a neutral ligand, showed cytotoxic activity against 12 out of 14 target cell lines. Their cytotoxic activity was similar or even slightly higher than that of the reference carboplatin. The remaining six compounds, coded 4-9, with 1-alkylimidazole as a neutral ligand, revealed rather low cytotoxic activity, and only against the cells of the human bladder cancer cell line Hu1703He, ovarian cancer cell line OAW-42 and mouse leukemia P388. Most of them appeared to be negative against all other cell lines. No compounds, including reference carboplatin, showed any cytotoxicity against the cells of the T47D human breast cancer cell line or B16F-10 mouse melanoma cell line. The results obtained are in accordance with common opinion, i.e. that the presence of neutral amine ligands with NH groups is required for the cytotoxic activity of platinum complexes. Compounds with a primary amine (ethylenediamine) showed higher cytotoxic activity in vitro than complexes with a tertiary amine (1alkylimidazole).
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw. opolski@immuno.iitd.pan.wroc.pl
A
A
Opolski
J
J
Kuduk-Jaworska
J
J
Wietrzyk
E
E
Wojdat
K
K
Waszkiewicz
A
A
Romaniewska
C
C
Radzikowski
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016190:Carboplatin / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D007942:Leukemia, Experimental / Q000188:drug therapy; D051379:Mice; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy; D014407:Tumor Cells, Cultured / Q000187:drug effects*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D016190:Carboplatin