Evaluation of in vitro cytotoxicity and hepatotoxicity of platinum(II) and palladium(II) oxalato complexes with adenine derivatives as carrier ligands.
In vitro antitumour activity of the [Pt(ox)(L(n))(2)] (1-7) and [Pd(ox)(L(n))(2)] (8-14) oxalato (ox) complexes involving N6-benzyl-9-isopropyladenine-based N-donor carrier ligands (L(n)) against ovarian carcinoma (A2780), cisplatin resistant ovarian carcinoma (A2780cis), malignant melanoma (G-361), lung carcinoma (A549), cervix epitheloid carcinoma (HeLa), breast adenocarcinoma (MCF7) and osteosarcoma (HOS) human cancer cell lines was studied. Some of the tested complexes were even several times more cytotoxic as compared with cisplatin employed as a positive control. The improved cytotoxic effect was demonstrated for the platinum(II) complexes 3 (IC(50)=3.2+/-1.0 microM and 3.2+/-0.6 microM) and 5 (IC(50)=4.0+/-1.0 microM and 4.1+/-1.4 microM) against A2780 and A2780cis, as compared with 11.5+/-1.6 microM, and 30.3+/-6.1 microM determined for cisplatin, respectively. The significant in vitro cytotoxicity against MCF7 (IC(50)=8.2+/-3.8 microM for 12) and A2780 (IC(50)=5.4+/-1.2 microM for 14) was evaluated for the palladium(II) oxalato complexes, which again exceeded cisplatin, whose IC(50) equalled 19.6+/-4.3 microM against the MCF7 cells. Selected complexes were also screened for their in vitro cytotoxic effect in primary cultures of human hepatocytes and they were found to be non-hepatotoxic.
Vrzal
Radim
R
Department of Cell Biology and Genetics, Faculty of Science, Palacký University, Olomouc, Czech Republic.
Starha
Pavel
P
Dvorák
Zdenek
Z
Trávnícek
Zdenek
Z
D000225:Adenine / Q000031:analogs & derivatives / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D016190:Carboplatin / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology; D006367:HeLa Cells; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D010165:Palladium / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry*
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D010984:Platinum; D010165:Palladium; D016190:Carboplatin; D000225:Adenine; D002945:Cisplatin