Synthesis, DNA-binding affinity and cytotoxicity of the dinuclear platinum(II) complexes with berenil and amines ligands.
A series of platinium(II) complexes of formula [Pt2L4(berenil)2]Cl4.4HCl.2H2O where L is piperidine (1), 4-picoline (2), 3-picoline (3) or isopropylamine (4) was prepared and their cytotoxicity have been tested against the growth of human breast cancer cells. Evaluation of the cytotoxicity of these compounds employing a MTT assay and inhibition of [3H]thymidine incorporation into DNA in both MDA-MB-231 and MCF-7 breast cancer cells demonstrated that these compounds were more active than cisplatin. Data from the ethidium displacement assay indicated that these compounds show moderate specificity for AT base pairs of DNA. Compounds 1-4 were also potent topoisomerase II inhibitors, with 50% inhibitory concentrations (IC50) ranging from 5 to 50 microM.
Bielawski
Krzysztof
K
Department of Medicinal Chemistry and Drug Technology, Medical University of Białystok, Białystok, Poland. kbiel@amb.edu.pl
Bielawska
Anna
A
Popławska
Bozena
B
Bołkun-Skórnicka
Urszula
U
D000588:Amines / Q000737:chemistry; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D020029:Base Pairing; D001943:Breast Neoplasms / Q000188:drug therapy*; D002417:Cattle; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D004133:Diminazene / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000008:administration & dosage / Q000138:chemical synthesis / Q000494:pharmacology; D004996:Ethidium / Q000378:metabolism; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000494:pharmacology; D013936:Thymidine / Q000378:metabolism; D059005:Topoisomerase II Inhibitors
D000588:Amines; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D008024:Ligands; D009944:Organoplatinum Compounds; D059005:Topoisomerase II Inhibitors; C110112:platinum-berenil; D004247:DNA; C427203:calf thymus DNA; D004996:Ethidium; D002945:Cisplatin; D013936:Thymidine; D004133:Diminazene