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. 1991 Jul;64(1):41–46. doi: 10.1038/bjc.1991.236

Comparison of the antitumour effects and nephrotoxicity-inducing activities of two new platinum complexes, (-)-(R)-2-aminomethylpyrrolidine(1,1-cyclobutanedicarboxylato+ ++)-platinum (II) monohydrate, and its enantiomeric isomer.

T Matsumoto 1, K Endoh 1, K Akamatsu 1, K Kamisango 1, H Mitsui 1, K Koizumi 1, K Morikawa 1, M Koizumi 1, T Matsuno 1
PMCID: PMC1977319  PMID: 1854626

Abstract

New platinum complexes, (-)-(R)-2-aminomethylpyrrolidine(1,1- cyclobutanedicarboxylato)platinum(II) monohydrate (DWA2114R) and its enantiomeric isomer, (+)-(S)-2-aminomethylpyrrolidine(1,1- cyclobutanedicarboxylato)platinum(II) monohydrate (DWA2114S), were compared in their antitumour effects and nephrotoxicity-inducing activities. Both compounds were effective against the murine tumours L1210 and Colon 26 by i.p. injection of 20-100 mg kg-1. While DWA2114S showed marked increases in blood urea nitrogen (BUN) and urinary protein and sugar in BDF1 mice treated i.p. at the maximum tolerated dose, DWA2114R showed no increases in these parameters. To clarify the difference of nephrotoxicity between the isomers, tissue distribution was examined. Renal Pt concentration in DWA2114S-treated mice was more than 5-fold higher compared with that in DWA2114R-treated mice 2h after i.p. injection of 80 mg kg-1. However, there were no such marked differences in the lung, liver, heart, spleen and plasma. The low content of Pt in the kidneys of DWA2114R-treated mice could explain its lower nephrotoxicity. The in vitro experiments for uptake of the drugs into the cultured normal rat kidney cells and fresh splenocytes revealed that the Pt amount in the cells treated with DWA2114S, especially in the kidney cells, was much higher than DWA2114R.

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Selected References

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  1. Bodenner D. L., Dedon P. C., Keng P. C., Katz J. C., Borch R. F. Selective protection against cis-diamminedichloroplatinum(II)-induced toxicity in kidney, gut, and bone marrow by diethyldithiocarbamate. Cancer Res. 1986 Jun;46(6):2751–2755. [PubMed] [Google Scholar]
  2. Burchenal J. H., Kalaher K., Dew K., Lokys L. Rationale for development of platinum analogs. Cancer Treat Rep. 1979 Sep-Oct;63(9-10):1493–1498. [PubMed] [Google Scholar]
  3. Byfield J. E., Calabro-Jones P. M. Carrier-dependent and carrier-independent transport of anti-cancer alkylating agents. Nature. 1981 Nov 19;294(5838):281–283. doi: 10.1038/294281a0. [DOI] [PubMed] [Google Scholar]
  4. Connors T. A., Cleare M. J., Harrap K. R. Structure-activity relationships of the antitumor platinum coordination complexes. Cancer Treat Rep. 1979 Sep-Oct;63(9-10):1499–1502. [PubMed] [Google Scholar]
  5. Cvitkovic E., Spaulding J., Bethune V., Martin J., Whitmore W. F. Improvement of cis-dichlorodiammineplatinum (NSC 119875): therapeutic index in an animal model. Cancer. 1977 Apr;39(4):1357–1361. doi: 10.1002/1097-0142(197704)39:4<1357::aid-cncr2820390402>3.0.co;2-c. [DOI] [PubMed] [Google Scholar]
  6. Endoh K., Akamatsu K., Matsumoto T., Morikawa K., Honda M., Mitsui H., Koizumi M., Koizumi K., Matsuno T. Antitumor activity of a new platinum complex, 2-aminomethyl-pyrrolidine (1, 1-cyclobutanedicarboxylato) platinum (II). Anticancer Res. 1989 Jul-Aug;9(4):987–991. [PubMed] [Google Scholar]
  7. Goldenberg G. J., Vanstone C. L., Israels L. G., Iise D., Bihler I. Evidence for a transport carrier of nitrogen mustard in nitrogen mustard-sensitive and -resistant L5178Y lymphoblasts. Cancer Res. 1970 Sep;30(9):2285–2291. [PubMed] [Google Scholar]
  8. Kidani Y., Inagaki K., Iigo M., Hoshi A., Kuretani K. Antitumor activity of 1,2-diaminocyclohexane--platinum complexes against sarcoma-180 ascites form. J Med Chem. 1978 Dec;21(12):1315–1318. doi: 10.1021/jm00210a029. [DOI] [PubMed] [Google Scholar]
  9. Krakoff I. H. Nephrotoxicity of cis-dichlorodiammineplatinum(II). Cancer Treat Rep. 1979 Sep-Oct;63(9-10):1523–1525. [PubMed] [Google Scholar]
  10. Lelieveld P., Van der Vijgh W. J., Veldhuizen R. W., Van Velzen D., Van Putten L. M., Atassi G., Danguy A. Preclinical studies on toxicity, antitumour activity and pharmacokinetics of cisplatin and three recently developed derivatives. Eur J Cancer Clin Oncol. 1984 Aug;20(8):1087–1104. doi: 10.1016/0277-5379(84)90112-3. [DOI] [PubMed] [Google Scholar]
  11. Litterst C. L., Gram T. E., Dedrick R. L., Leroy A. F., Guarino A. M. Distribution and disposition of platinum following intravenous administration of cis-diamminedichloroplatinum(II) (NSC 119875) to dogs. Cancer Res. 1976 Jul;36(7 Pt 1):2340–2344. [PubMed] [Google Scholar]
  12. Osman N. M., Copley M. P., Litterst C. L. Amelioration of cisplatin-induced nephrotoxicity by the diuretic acetazolamide in F344 rats. Cancer Treat Rep. 1984 Jul-Aug;68(7-8):999–1004. [PubMed] [Google Scholar]
  13. Pera M. F., Jr, Harder H. C. Analysis for platinum in biological material by flameless atomic absorption spectrometry. Clin Chem. 1977 Jul;23(7):1245–1249. [PubMed] [Google Scholar]
  14. Prestayko A. W., Bradner W. T., Huftalen J. B., Rose W. C., Schurig J. E., Cleare M. J., Hydes P. C., Crooke S. T. Antileukemia (L1210) activity and toxicity of cis-dichlorodiammineplatinum(II) analogs. Cancer Treat Rep. 1979 Sep-Oct;63(9-10):1503–1508. [PubMed] [Google Scholar]
  15. Rozencweig M., von Hoff D. D., Slavik M., Muggia F. M. Cis-diamminedichloroplatinum (II). A new anticancer drug. Ann Intern Med. 1977 Jun;86(6):803–812. doi: 10.7326/0003-4819-86-6-803. [DOI] [PubMed] [Google Scholar]
  16. Vistica D. T., Toal J. N., Rabinovitz M. Amino acid-conferred protection against melphalan--characterization of melphalan transport and correlation of uptake with cytotoxicity in cultured L1210 murine leukemia cells. Biochem Pharmacol. 1978;27(24):2865–2870. doi: 10.1016/0006-2952(78)90202-2. [DOI] [PubMed] [Google Scholar]
  17. Von Hoff D. D., Schilsky R., Reichert C. M., Reddick R. L., Rozencweig M., Young R. C., Muggia F. M. Toxic effects of cis-dichlorodiammineplatinum(II) in man. Cancer Treat Rep. 1979 Sep-Oct;63(9-10):1527–1531. [PubMed] [Google Scholar]
  18. Ward J. M., Grabin M. E., Berlin E., Young D. M. Prevention of renal failure in rats receiving cis-diamminedichloroplatinum(II) by administration of furosemide. Cancer Res. 1977 Apr;37(4):1238–1240. [PubMed] [Google Scholar]

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