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Metal Chelates of 3-Ethoxy-2-Oxobutyraldehyde Bis (Thiosemicarbazone), H2KTS

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Abstract

Interest in the chemotherapeutic activity of thiosemicarbazones stems from the discovery of Domagk et al. (1946) that certain monothiosemicarbazones have antitubercular action. Since then, a great many mono- and dithiosemicarbazones have been synthesized and assayed for possible chemotherapeutic activity in a number of systems. Among these compounds are a number of bis(thiosemicarbazones) of α-ketoaldehydes or diketones which have been found to show antimicrobial, antiparasitic, and antitumor activities (Barrett et al., 1965; Michaels et al., 1962; French and Freedlander, 1958; Barry et al., 1970).

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References

  • Bähr, G.: Über Emprotide Schwermetall-Inner-Complexe Der α-Diketon-Dithiosemicarbazone (Thiazone). I. Z. f. Anorg. Allg. Chemie 268, 351–363 (1952).

    Article  Google Scholar 

  • Bähr, G.: Über Emprotide Schwermetall-Inner-Complexe Der α-Diketon-Dithiosemicarbazone (Thiazone). II. Z. f. Anorg. Allg. Chemie 273, 325–332 (1953).

    Article  Google Scholar 

  • Barrett, P. A., Beveridge, E., Bradley, P. L., Brown, C. G. D., Bushby, S. R. M., Clarke, M. L., Neal, R. A., Smith, R., Wilde, J. K. H.: Biological activities of some α-Dithiosemi- Carbazones. Nature (Lond.) 206, 1340–1341 (1965).

    Article  CAS  Google Scholar 

  • Barry, V. C., Conalty, M. L., McCormick, J. E., McElhenney, K. S., Mcinerney, M. R., O’sullivan, J. F.: Anticancer agents. IV. The antitumor activity of some 1,4- and 1,5- (bisthiosemicarbazones) and of related heterocycles. J. med. Chem. 13, 421–427 (1970).

    Google Scholar 

  • Booth, B. A., Donnelly, T.E., Jr., Zettner, A., Sartorelli, A.C.: Metabolic effects of zinc in intact cells—comparative studies of zinc chloride and the zinc chelate of kethoxal bis- (thiosemicarbazone). Biochem. Pharmacol. 20, 3109–3118 (1971).

    Google Scholar 

  • Booth, B. A., Johns, D.G., Bertino,J.R., Sartorelli,A.C.: Sites of inhibition of DNA synthesis by kethoxal bis(thiosemiearbazone). Nature (Lond.) 217, 250–251 (1968).

    Google Scholar 

  • Booth, B. A., Sartorelli, A. C.: Synergistic interaction of kethoxal bis(thiosemicarbazone) and cupric ions in Sarcoma 180. Nature (Lond.) 210, 104–105 (1966).

    Google Scholar 

  • Booth, B. A., Sartorelli, A. C.: Metabolic effects of copper in intact cells: comparative activity of cupric chloride and the cupric chelate of kethoxal bis(thiosemicarbazone). Molec. Pharmacol. 3, 290–302 (1967).

    CAS  Google Scholar 

  • Crim, J. A., Petering, H.G.: The antitumor activity of Cu(II)KTS, the copper (II) chelate of 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazone). Cancer Research 27, 1278–1285

    Google Scholar 

  • Domagk, G., Behnisch, R., Mietzsch, F., Schmidt, H.: Über eine neue, gegen Tuberkelbazillen in vitro wirksame Verbindungsklasse. Naturwissenschaften 33, 315 (1946).

    Article  CAS  Google Scholar 

  • French, P. A., Freedlander, B. L.: Carcinostatic action of polycarbonyl compounds and their derivatives. IV. Glyoxal bis(thiosemicarbazone) and derivatives. Cancer Res. 18, 1298–1300 (1958).

    Google Scholar 

  • French, F. A., Freedlander, B. L.: Chemotherapy studies on transplanted tumors. Cancer Res. 21, 505–538 (1960).

    Google Scholar 

  • Gingras, B. A., Hornal, R.W., Bayley, C.H.: The preparation of some thiosemicarbazones and their copper complexes. I. Canad. J. Chem. 38, 712–719 (1960).

    Article  CAS  Google Scholar 

  • Gingras, B. A., Somarjai, R.L., Bayley, C.H.: The preparation of some thiosemicarbazones and their copper complexes. II. Canad. J. Chem. 39, 973–985 (1961).

    Article  CAS  Google Scholar 

  • Gingras, B. A., Suprunchuk, T., Bayley, C. H: The preparation of some thiosemicarbazones and their copper complexes. III. Canad. J. Chem. 40, 1053–1059 (1962).

    Article  CAS  Google Scholar 

  • Martin, D. S.: Combination adjuvant therapy after surgery for spontaneous breast tumors. Proc. Amer. Ass. Cancer. Res. 4, 42 (1963).

    Google Scholar 

  • Mcquitty, J. T., Dewys, W. D., Monaco, L., Strain, W. H., Rob, C. G., Apgar, J., Pories, W. J.: Inhibition of tumor growth by dietary zinc deficiency. Cancer Res. 30, 1387–1390 (1970).

    PubMed  CAS  Google Scholar 

  • Michaels, R. M., Peterson, L. J., Stahl, G.L.: The activity of substituted thiosemicarbazones against T. vaginalis and T. foetus in vitro and in experimental animals. J. Parasitol. 48, 891–897 (1962).

    Article  PubMed  CAS  Google Scholar 

  • Mihich, E., Mulhern, A. I.: Comparative potency of kethoxal bis(thiosemicarbazone) (KTS) and its copper II chelate (KTS—Cu) in rodents. Fed. Proc. 24, 454 (1965).

    Google Scholar 

  • Mihich, E., Niöhol, C. A.: Enhanced inhibition of Sarcoma 180 (S180) caused by methyl- glyoxal-bis(N4-methylthiosemicarbazone) (CH3—GMS) and dietary pyridoxine deficiency. Proc. Amer. Ass. Cancer Res. 3, 250 (1961).

    Google Scholar 

  • Mihich, E., Nichol, C. A.: Kethoxal bis(thiosemicarbazone). I. Effects against experimental tumors. Cancer Res. 25, 1410–1416 (1965).

    PubMed  CAS  Google Scholar 

  • Mihich, E., Simpson, C. L.: Comparative study of α-n-butyryloxyethylglyoxal bis(thiosemi- carbazone) (BGTS) and kethoxal-bis(thiosemicarbazone) (KTS). Pharmacologist 10, 171

    Google Scholar 

  • Mihich, E., Simpson, C. L., Mulhern, A. I.: Kethoxal bis(thiosemicarbazone). II. Toxic and pathologic effects. Cancer Res. 25, 1417–1431 (1965).

    Google Scholar 

  • Nettberg, C., Neimann, W.: Eine Methode zur Isolierung von Aldehyden und Ketonen. Ber. 35, 2049–2056 (1902).

    Google Scholar 

  • Petering, D. H.: CuKTS. I. Physico-chemical properties of the antitumor agent. Bioinorg. Chem. I, 255–271 (1972a).

    Google Scholar 

  • Petering, D. H.: CuKTS. II. Reactions with thiols. Bioinorg. Chem., I, 273–288 (1972b).

    Google Scholar 

  • Petering, D. H.: The role of zinc in the antitumor activity of 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazonato)zinc (II) and related compounds. Biochem. Pharmacol. 23, 567–576 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Petering, H. G., Buskirk, H. H.: The antitumor activity of 2-ke to-3-ethoxybutyraldehyde bis(thiosemicarbazone) and related compounds. Fed. Proc. 21, 163 (1962).

    Google Scholar 

  • Petering, H. G., Buskirk, H. H., Crim, J. A.: Activity of combinations of uracil mustard (NSC-34462) and 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazone) (KTS, NSC-82116) against murine tumors. Cancer Chemother. Rep. 50, 557–563 (1966 a).

    Google Scholar 

  • Petering, H. G., Buskirk, H. H., Crim, J. A.: The effect of dietary mineral supplements of the rat on the antitumor activity of 3-ethoxy-2-oxobutyraldehyde (thiosemicarbazone). Cancer Res. 27, 1115–1121 (1967).

    PubMed  CAS  Google Scholar 

  • Petering, H. G., Buskirk, H. H., Crim, J.A., Van Giessen, G. J.: The effect of essential metal ions on the antitumor activity of kethoxal bis(thiosemicarbazone) (KTS). Pharmacologist 5, 271 (1963).

    Google Scholar 

  • Petering, H. G., Buskirk, H. H., Kupiecki, F.: Chelate formation and antitumor activity of KTS. Fed. Proc. 24, 454 (1965).

    Google Scholar 

  • Petering, H. G., Buskirk, H. H., Underwood, G. E.: The antitumor activity of 2-keto-3- ethoxybutyraldehyde bis(thiosemicarbazone) and related compounds. Cancer Res. 24, 367–372 (1964).

    PubMed  CAS  Google Scholar 

  • Petering, H. G., Van Giessen, G. J.: The essential role of cupric ion in the biological activity of 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazone), a new antitumor agent. In: Piesach, Aisen, Blumberg (Eds.): The biochemistry of copper, pp. 197–210. New York: Academic Press 1966 b.

    Google Scholar 

  • Petering, H. G., Van Giessen, G. J., Crim, J. A., Buskirk, H. H.: The synthesis and antitumor activity of several thiosemicarbazones related to kethoxal bis(thiosemicarbazone). J. med. Chem. 9, 420–421 (1966 c).

    Google Scholar 

  • Regelson, W., Holland, J. F., Talley, R. W.: Clinical pharmacologic study of kethoxal bis- (thiosemicarbazone) (NSC-82116) in advanced cancer. Cancer Chemother. Rep. 51, 171–177 (1967).

    PubMed  CAS  Google Scholar 

  • Sabtobelli, A. C., Welch, A. D., Booth, B. A.: Biochemical effects of kethoxal bis(thiosemicarbazone) and its cupric chelate. Fed. Proc. 24, 454 (1965).

    Google Scholar 

  • Van Giessen, G. J., Crim, J. A., Petering, D. H., Petering, H. G.: Effect of heavy metals on the in vitro cytotoxicity of 3-ethoxy-2-oxobutyraldehyde bis(thiosemicarbazone) and related compounds. J. nat. Cancer Inst. 51, 139–146 (1973).

    PubMed  Google Scholar 

  • Van Giessen, G. J., Petering, H. G.: Metal complexes of 3-ethoxy-2-oxobutyraldehyde bis-(thiosemicarbazone) and related ligands as antitumor agents. J. med. Chem. 11, 695–699 (1968).

    Article  PubMed  Google Scholar 

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Authors
  1. David H. Petering
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  2. Harold G. Petering
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Editors and Affiliations

  1. Department of Pharmacology, Yale University School of Medicine, 06510, New Haven, Connecticut, USA

    Alan C. Sartorelli (Professor) (Professor)

  2. Laboratory of Chemical Pharmacology, National Cancer Institute, National Institutes of Health, 20014, Bethesda, Maryland, USA

    David G. Johns M.D.

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© 1975 springer-Verlag Berlin-Heidelberg

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Petering, D.H., Petering, H.G. (1975). Metal Chelates of 3-Ethoxy-2-Oxobutyraldehyde Bis (Thiosemicarbazone), H2KTS. In: Sartorelli, A.C., Johns, D.G. (eds) Antineoplastic and Immunosuppressive Agents. Handbuch der experimentellen Pharmakologie / Handbook of Experimental Pharmacology, vol 38 / 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-65806-8_48

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  • DOI: https://doi.org/10.1007/978-3-642-65806-8_48

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-65808-2

  • Online ISBN: 978-3-642-65806-8

  • eBook Packages: Springer Book Archive

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