Preparation of antitumor oxaliplatin/cisplatin docking dinuclear platinum complex.
A new dinuclear docking Pt(II) complex, (cis-diammine) (l-1,2-cyclohexanediamine)(mu-dichloro)-diplatinum(II) oxalate was synthesized by reacting oxaliplatin(l-OHP, [Pt(oxalato)(L-dach)]), L-dach = 1R, 2R-cyclohexanediamine), with cisplatin (CDDP). Elemental analysis of the compound indicated that it was 1:1 molar ratio complex of oxaliplatin and cisplatin. A plausible chemical structure has been proposed as Cl(-) bridged dinuclear complex, judged from its yellow coloration and NMR spectral analysis. This complex can be denoted as, i.e. [Pt(2)Cl(2)(NH(3))(2)(L-dach)](COO)(2) (L-OHP/CDDP). The complex showed higher cytotoxicity against L1210 than the parent complexes and low cross-resistance against L1210/CDDP and L1210/DACH. Its antitumor activity was also tested in vivo against murine leukemia L1210 cell lines. The complex showed much higher activity than the mixture(1:1 molar ratio) of oxaliplatin and cisplatin. The antitumor effect against L1210/CDDP was very high, showing collateral sensitivity, being similar to that of oxaliplatin, and against L1210/DACH it showed no cross-resistance.
Noji
Masahede
M
Suzuka University of Medical Science, 1001-1 Kishioka-cho, Suzuka, Mie 510-0293, Japan. noji@suzuka-u.ac.jp
Kizu
Ryoichi
R
Takeda
Yasutaka
Y
Akiyama
Nachio
N
Yoshizaki
Iwao
I
Eriguchi
Masazumi
M
Kidani
Yoshinori
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000737:chemistry*; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D015394:Molecular Structure; D009368:Neoplasm Transplantation; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D000077150:Oxaliplatin
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C503558:diammine(1,2-cyclohexanediamine)(mu-dichloro)diplatinum(II); D000077150:Oxaliplatin; D002945:Cisplatin