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New derivatives of CNC-amino acids and -oligopeptides: Experimental antitumor activity

  • Original Papers
  • Experimental Oncology
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Summary

The experimental antitumor activity of a series of new nitrosoureas is described in which the chloroethylnitrosocarbamoyl (CNC) group is attached to different carrier molecules: amino acids and oligopeptides.

Of a group of 10 CNC-amino acid amide derivatives the majority displayed high therapeutic activity in L 5222 leukemia. Some compounds, especialy the proline and sarcosine derivatives, showed favorable therapeutic ratios; 12 CNC-oligopeptides displayed a more or less pronounced therapeutic activity in L 1210 leukemia. Compounds bearing a free carboxy group were less active than the corresponding unsubstituted or N-methyl substituted amides.

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References

  • Cleare MJ (1984) Further objectives in the development of platinum drugs. In: Harrap KR, Davis W, Calvert AH (eds) Cancer chemotherapy and selective drug development. Nijhoff, Boston pp 357–362

    Google Scholar 

  • Ehresmann K (1985) Synthese und Eigenschaften cytostatisch wirksamer 2-Chloroethylnitrosoharnstoffe. Inaug Diss, University Heidelberg

  • Ehresmann K, Zelezny O, Eisenbrand G (1984) Syntheses of potentially antineoplastic amides and esters of N-[N′(2-chloroethyl)-N′-nitrosocarbamoyl] amino acids, II. Arch Pharm 317:481–487

    Google Scholar 

  • Eisenbrand G, Habs M, Zeller WJ, Fiebig H, Berger M, Zelezny O, Schmähl D (1981) New Nitrosoureas — therapeutic and long-term toxic effects of selected compounds in comparison to established drugs. In: Serrou B, Schein PS, Imbach JL (eds) Nitrosoureas in cancer treatment. Elsevier, Amsterdam, pp 175–191

    Google Scholar 

  • Eisenbrand G, Tang W, Zelezny O (1983) N-(N′-(2-Chloräthyl)-N′-nitroso-carbamoyl)-oligopeptidester und-amide und Verfahren zu ihrer Herstellung. EP 0 074 103 A1 (Int. Cl. C 07 C103/52)

  • Fujimoto S, Ogawa M (1982) A new nitrosourea derivative TA-077, 1-(2-chloroethyl)-3-isobutyl-3-(β-maltosyl)-1-nitrosourea. I. Comparative study on antitumor activity. Cancer Chemother Pharmacol 9:134–139

    PubMed  Google Scholar 

  • Johnston TP, McCaleb GS, Montgomery JA (1975) Synthesis of chlorozotocin, the 2-chloroethyl analog of the anticancer antibiotic streptozotocin. J Med Chem 18:104–106

    PubMed  Google Scholar 

  • Mori KJ, Jasmin C, Hayat M, MacDonald JS, Mathé G (1980) In vivo study of acute hematotoxicity of three nitrosoureas, chlorozotocin, (chloro-2-ethyl)-ribofuranosyl-3-nitrosourea, and (chloro-2-ethyl)-1-ribopyranosyl-3-nitrosourea. Cancer Res 40:4282–4286

    PubMed  Google Scholar 

  • Ogawa M (1981) Current status of nitrosoureas under development in Japan. In: Prestayko AW et al. (eds) Nitrosoureas. Current status and new developments Acad Press, New York, pp 399–409

    Google Scholar 

  • Schein PS, McMenamin M, Anderson T (1973) 3-(Tetra-acetylglucopyranose-2-yl)-1-(2-chloroethyl)-1-nitrosourea, an antitumor agent with modified bone marrow toxicity. Cancer Res 33:2005–2009

    PubMed  Google Scholar 

  • Suami T, Kato T, Takino H, Hisamatsu T (1982) 2-Chloroethyl-nitrosourea congeners of amino acid amides. J Med Chem 25:829–832

    PubMed  Google Scholar 

  • Tang W, Eisenbrand G (1981) Synthesis of potentially antineoplastic derivatives of N-[N-(2-chloroethyl)-N-nitrosocarbamoyl] amino acids. Arch Pharm 314:910–917

    Google Scholar 

  • Zeller WJ, Eisenbrand G, Fiebig HH (1979) Examination of four newly synthesized 2-chloroethylnitrosoureas in comparison with BCNU, CCNU, MeCCNU, chlorozotocin and hydroxyethyl-CNU in preterminal rat leukemia L5222. J Cancer Res Clin Oncol 95:43–49

    PubMed  Google Scholar 

  • Zeller WJ, Berger M, Eisenbrand G, Tang W, Schmähl D (1982) Chemotherapeutic activity of 2-chloroethylnitrosocarbamoyl derivatives of amino acids in a transplanted rat leukemia (L5222). Arzneimittelforsch 32:484–486

    PubMed  Google Scholar 

  • Zeller WJ, Ehresmann K, Eisenbrand G (1984a) Antineoplastic activity of estrs and amides of N-[N′-(2-Chloroethyl)-N′-nitrosocarbamoyl]-aminoacids. J Cancer Res Clin Oncol 108:249–251

    PubMed  Google Scholar 

  • Zeller WJ, Schreiber J, Ho AD, Schmähl D, Eisenbrand G (1984b) Cytostatic activity of steroid linked nitrosoureas. J Cancer Res Clin Oncol 108:164–168

    PubMed  Google Scholar 

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Dedicated to Professor Dietrich Schmähl on the occasion of his 60th birthday

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Zeller, W.J. New derivatives of CNC-amino acids and -oligopeptides: Experimental antitumor activity. J Cancer Res Clin Oncol 111, 154–156 (1986). https://doi.org/10.1007/BF00400755

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  • DOI: https://doi.org/10.1007/BF00400755

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