Abstract
Water‐miscible platinum(II) complexes with 1,2‐diaminocyclohexane as the carrier ligand and bile acids as the leaving ligands were synthesized and tested for antitumor activity against intra‐peritoneally implanted leukemia L1210 cells in mice. These complexes were water‐miscible after appropriate sonication due to the presence of hydrophilic hydroxyl groups in the molecule, even though the complexes were essentially lipophilic. The complexes had high antitumor activity, but their optimal dose levels differed, and the administration route and form affected the antitumor activity. More lipophilic complexes showed higher activity when administered with Lipiodol than in water suspension, while the hydrophilic complexes showed significant activity when administered in water suspension. Intravenous administration of DACHP(cheno)2 in water suspension resulted in potent antitumor activity, while other complexes showed moderate activity via this route.
Keywords: Liposoluble platinum(II) complexes; 1,2‐Cyclohexanediammineplatinum(II); Bile acid derivatives; Micelle‐forming platinum(II) complexes; Water‐miscible platinum(II) complexes
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REFERENCES
- 1. ) Rosenberg , B. , VanCamp , L. , Trosko , J. F. and Mansour , V. H. Platinum compounds: a new class of potent anti‐tumor agents . Nature , 222 , 385 – 386 ( 1969. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Prestayko , A. W. , D'Aoust , J. C. , Issell , B. F. and Crooke , S. T. Cisplatin (cis‐diamminedichloroplatinum II) . Cancer Treat. Rev. , 6 , 17 – 39 ( 1979. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Cleare , M. J. and Hoeschele , J. D. Antitumor platinum compounds. Relationship between structure and activity . Platinum Metals Rev. , 17 , 2 – 13 ( 1973. ). [Google Scholar]
- 4. ) Connors , T. A. , Jones , M. , Ross , W. C. J. , Braddock , P. D. , Khokhar , A. R. and Tobe , M. L. New platinum complexes with antitumor activity . Chem.-Biol. Interact. , 5 , 415 – 424 ( 1972. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Hacker , M. P. , Khokhar , A. R. , Brown , D. B. , McCormack , J. J. and Krakoff , I. H. Ascorbato(1,2‐diaminocyclohexane): platinum(II) complexes . Cancer Res. , 45 , 4748 – 4753 ( 1985. ). [PubMed] [Google Scholar]
- 6. ) Maeda , M. , Abiko , N. and Sasaki , T. Synthesis and antitumor activity of cis‐dichloroplatinum(II)‐N‐aminated nucleoside complexes . J. Med. Chem. , 27 , 444 – 449 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Maeda , M. , Abiko , N. and Sasaki , T. Synthesis of seleno‐ and thio‐guanine platinum(II) complexes and their anti‐tumor activity in mice . J. Med. Chem. , 24 , 167 – 169 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 8. ) Maeda , M. , Uchida , N. A. and Sasaki , T. Liposoluble platinum(II) complexes with antitumor activity . Jpn. J. Cancer Res. , 77 , 523 – 525 ( 1986. ). [PubMed] [Google Scholar]
- 9. ) Ridgway , H. J. , Speer , H. J. , Hall , L. M. , Stewart , D. P. , Newman , A. D. and Hill , J. M. Analogs of sulfato‐1,2‐diaminocyclohexane platinum(II). I. Modifications in leaving ligand . J. Clin. Oncol. Hematol. , 7 , 220 – 230 ( 1977. ). [Google Scholar]