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Chemical Compound Review

Spirogermanio     3-(8,8-diethyl-3-aza-8...

Synonyms: SPIROGERMANIUM, Spiro 32, NCIMech_000382, CCG-35966, Neuro_000106, ...
 
 
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Disease relevance of Spirogermanium compound

 

High impact information on Spirogermanium compound

  • When spirogermanium was tested against a range of human cell lines, the consistency of the values for the drug concentration required to reduce survival by 50% on the exponential part of the survival curve, derived from colony-forming assays, was most marked [6].
  • Lethal and other biological effects of 2-aza-8-germanspiro[4,5]decane-2-propanamine-8,8-diethyl-N,N-dimethyl dichloride (NSC 192965; spirogermanium), representing a new chemical class of compound exhibiting antitumor activity, have been studied in vitro [6].
  • Cell membrane damage by spirogermanium, as judged by dye exclusion, was progressive with time and increasing drug concentrations [6].
  • This structure-activity relationship study has identified that appropriately substituted silicon and carbon analogues of spirogermanium retain both antiarthritic and immunosuppressive activity, with the 8,8-dipropyl (carbon) analogue being among the most active [7].
  • An evaluation of combination 5-fluorouracil and spirogermanium in the treatment of advanced colorectal carcinoma [8].
 

Chemical compound and disease context of Spirogermanium compound

 

Biological context of Spirogermanium compound

  • Although its mode of action has not been fully elucidated, it appears that spirogermanium is not a phase or cell cycle specific drug and inhibits DNA, RNA and protein synthesis, the protein synthesis being the most susceptible to this agent [12].
  • Thirty-three patients with advanced malignancy were treated with oral spirogermanium in a Phase I study to determine a maximum tolerated dose [13].
  • A series of continuous human tumour cell lines, derived from various tumour types, were used to establish whether the combination of spirogermanium (SP) with other 'standard' antitumour drugs proved superior to these as single agents in reducing cell survival in vitro [14].
  • Spirogermanium is remarkable for its lack of bone marrow toxicity confirmed in preclinical toxicology and clinical studies; moderate, predictable, and reversible CNS toxicity is dose-limiting [12].
  • The only active nongold organometallic complex was spirogermanium which had an equivalent IC50 for activity as AF [15].
 

Anatomical context of Spirogermanium compound

 

Associations of Spirogermanium compound with other chemical compounds

 

Gene context of Spirogermanium compound

  • Spirogermanium was also able to overcome the multidrug resistance exhibited by the colchicine-resistant mutant CHRC5 cells and a subline of vincristine-resistant MCF-7 human breast carcinoma cells, following 1 or 24 hour drug treatments [21].
  • Spirogermanium normalized these changes to various degrees, with the exception of the depressed IL-2 and IL-3 production [16].
  • Spirogermanium (SG) is a metal-containing compound reported to have antitumor, antiarthritic, antimalarial and immunoregulatory activity [22].
 

Analytical, diagnostic and therapeutic context of Spirogermanium compound

References

  1. Phase I study of spirogermanium given daily. Legha, S.S., Ajani, J.A., Bodey, G.P. J. Clin. Oncol. (1983) [Pubmed]
  2. Preliminary study on the suppression of experimental autoimmune encephalomyelitis in the Lewis rat with spirogermanium. Sacks, H.J., Braunstein, V., Brosnan, C.F. J. Neuropathol. Exp. Neurol. (1987) [Pubmed]
  3. A phase II study of spirogermanium in patients with advanced malignant lymphoma. Sessa, C., ten Bokkel Huinik, W., Clavel, M., Lev, L.M., Joss, R.A., Renard, J., Cavalli, F. Investigational new drugs. (1989) [Pubmed]
  4. Phase II study of spirogermanium in patients with advanced colorectal carcinoma. Ajani, J.A., Faintuch, J.S., McClure, R.K., Levin, B., Boman, B.M., Krakoff, I.H. Investigational new drugs. (1986) [Pubmed]
  5. A phase II study of spirogermanium in patients with metastatic malignant melanoma. An NCI Canada Clinical Trials Group Study. Eisenhauer, E., Kerr, I., Bodurtha, A., Iscoe, N., McCulloch, P., Pritchard, K., Quirt, I. Investigational new drugs. (1985) [Pubmed]
  6. Cytotoxic effects and biological activity of 2-aza-8-germanspiro[4,5]-decane-2-propanamine-8,8-diethyl-N,N-dimethyl dichloride (NSC 192965; spirogermanium) in vitro. Hill, B.T., Whatley, S.A., Bellamy, A.S., Jenkins, L.Y., Whelan, R.D. Cancer Res. (1982) [Pubmed]
  7. Antiarthritic and suppressor cell inducing activity of azaspiranes: structure-function relationships of a novel class of immunomodulatory agents. Badger, A.M., Schwartz, D.A., Picker, D.H., Dorman, J.W., Bradley, F.C., Cheeseman, E.N., DiMartino, M.J., Hanna, N., Mirabelli, C.K. J. Med. Chem. (1990) [Pubmed]
  8. An evaluation of combination 5-fluorouracil and spirogermanium in the treatment of advanced colorectal carcinoma. McMaster, M.L., Greco, F.A., Johnson, D.H., Hainsworth, J.D. Investigational new drugs. (1990) [Pubmed]
  9. Phase II study of n-methylformamide (NSC 3051) and spirogermanium (NSC 192965) in the treatment of advanced small cell lung cancer. Ettinger, D.S., Finkelstein, D.M., Abeloff, M.D., Chang, Y.C., Smith, T.J., Oken, M.M., Ruckdeschel, J.C. Investigational new drugs. (1990) [Pubmed]
  10. Complexes of metals other than platinum as antitumour agents. Köpf-Maier, P. Eur. J. Clin. Pharmacol. (1994) [Pubmed]
  11. An Eastern Cooperative Oncology Group phase II study of single agent DHAD, VP-16, aclacinomycin, or spirogermanium in metastatic pancreatic cancer. Asbury, R.F., Cnaan, A., Johnson, L., Harris, J., Zaentz, S.D., Haller, D.G. Am. J. Clin. Oncol. (1994) [Pubmed]
  12. Spirogermanium: a new investigational drug of novel structure and lack of bone marrow toxicity. Slavik, M., Blanc, O., Davis, J. Investigational new drugs. (1983) [Pubmed]
  13. Phase I study of oral spirogermanium. Harvey, J., McFadden, M., Smith, F.P., Joubert, L., Schein, P.S. Investigational new drugs. (1990) [Pubmed]
  14. Identification of synergistic combinations of spirogermanium with 5-fluorouracil or cisplatin using a range of human tumour cell lines in vitro. Hill, B.T., Bellamy, A.S., Metcalfe, S., Hepburn, P.J., Masters, J.R., Whelan, R.D. Investigational new drugs. (1984) [Pubmed]
  15. Effect of metal containing compounds on superoxide release from phorbol myristate acetate stimulated murine peritoneal macrophages: inhibition by auranofin and spirogermanium. Mirabelli, C.K., Sung, C.P., Picker, D.H., Barnard, C., Hydes, P., Badger, A.M. J. Rheumatol. (1988) [Pubmed]
  16. Antiarthritic and immunoregulatory activity of spirogermanium. DiMartino, M.J., Lee, J.C., Badger, A.M., Muirhead, K.A., Mirabelli, C.K., Hanna, N. J. Pharmacol. Exp. Ther. (1986) [Pubmed]
  17. Spirogermanium: effects on hematopoietic stem cells and survival of normal and tumor-bearing mice. Schwartz, G.N., Biegel, J.A., Fisher, B., Klein, I. Proc. Soc. Exp. Biol. Med. (1983) [Pubmed]
  18. Phase II protocol for the evaluation of new treatments in patients with advanced gastric carcinoma: results of ECOG 5282. Novik, Y., Ryan, L.M., Haller, D.G., Asbury, R., Dutcher, J.P., Schutt, A. Med. Oncol. (1999) [Pubmed]
  19. Trypanosoma cruzi: inhibition by spirogermanium hydrochloride. Tanowitz, H.B., Brennessel, D.J., Baum, S.G., Salgo, M.P., Braunstein, V., Wittner, M. Exp. Parasitol. (1987) [Pubmed]
  20. Comparison of antitumor activity of standard and investigational drugs at equivalent granulocyte-macrophage colony-forming cell inhibitory concentrations in the adhesive tumor cell culture system: an in vitro method of screening new drugs. Fan, D., Ajani, J.A., Baker, F.L., Tomasovic, B., Brock, W.A., Spitzer, G. European journal of cancer & clinical oncology. (1987) [Pubmed]
  21. Spirogermanium--a novel antitumour agent expressing a lack of cross-resistance in vitro with a range of 'standard' antitumour drugs. Hill, B.T., Whelan, R.D. Investigational new drugs. (1986) [Pubmed]
  22. Immunomodulatory activity and non-specific suppressor cell generation by spirogermanium in murine and rat models of cell-mediated immunity. Badger, A.M., DiMartino, M.J., Swift, B.A., Mirabelli, C.K. Immunopharmacology (1988) [Pubmed]
  23. Generation of suppressor cells in normal rats by treatment with spirogermanium, a novel heterocyclic anticancer drug. Badger, A.M., Mirabelli, C.K., DiMartino, M. Immunopharmacology (1985) [Pubmed]
  24. Determination of spirogermanium (2-aza-8-germanspiro[4.5]-decane-2-propanamine-8,8-diethyl-N,N-dimethyl dichloride) by fluorometric ion-pair extraction. Application to the uniformity of content of solutions for intravenous injection. Riley, C.M., Monnot, E.A., Stobaugh, J.F., Slavik, M. Journal of pharmaceutical and biomedical analysis. (1989) [Pubmed]
  25. Inhibition of autoimmune disease and the generation of suppressor cells by spirogermanium: a biological profile similar to total lymphoid irradiation. Badger, A.M., Mirabelli, C.K., Swift, B.A., DiMartino, M.J. Agents Actions (1989) [Pubmed]
 
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