An orally active antitumor cyclohexanediamine-Pt(IV) complex: trans,cis,cis-bis(n-valerato)(oxalato)(1R,2R-cyclohexane diamine)Pt(IV).
In order to develop orally active antitumor platinum complexes, several cyclohexanediamine-Pt(IV) complexes of a general formula trans,cis,cis-[Pt(IV) (OCOCnHn+1)2 (oxalato)(1R,2R-cyclohexanediamine)] were synthesized by derivatizing oxaliplatin [Pt(II)(oxalato)(1R,2R-cyclohexanediamine), I-OHP], which is a potent antitumor cyclohexanediamine-Pt(II) complex we have prepared and now undergoing clinical trials. The I-OHP derivatives were found to be stable, lipophilic and reduced to yield I-OHP, an active species, quantitatively by ascorbate in vitro. All the derivatives were antitumor active against mouse lymphocytic leukemia L1210 when given i.p. In particular, trans-bis-valerato-oxalato-1R,2R-dach-Pt(IV), C5-OHP, showed markedly high activity. C5-OHP also exhibited significant antitumor activity against L1210 when orally administered. C5-OHP was considered to be a suitable candidate for the oral cancer chemotherapy agent to be developed.
Kizu
R
R
Faculty of Pharmaceutical Sciences, Kanazawa University, Japan.
Nakanishi
T
T
Miyazaki
M
M
Tashiro
T
T
Noji
M
M
Matsuzawa
A
A
Eriguchi
M
M
Takeda
Y
Y
Akiyama
N
N
Kidani
Y
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001205:Ascorbic Acid; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D012995:Solubility; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C105372:bis-valerato-oxalato-1,2-diaminocyclohexaneplatinum; D001205:Ascorbic Acid