Colchicine Analogues in Experimental Murine Amyloidogenesis
Colchicine is a widely used preparation in diverse clinical settings such as gout, familial Mediterranean fever, AA amyloidosis, liver fibrosis and Bechet’s disease. It also has an antimitotic potential hitherto unexplored due to its narrow therapeutic toxic ratio.
Data is presented on the effectiveness and toxicity of three colchicine analogues: thiocolchicine, 2, 3 didemethylcolchicine and 3-demethyl-thiocolchicine in the blockage of amyloid synthesis in a murine model.
3-Demethylthiocolchicine was found as effective as colchicine in blocking anyloidogenesis. Doses three times higher than those of colchicine were well tolerated. The other two compounds were either less effective or toxic.
3-Demethylthiocolchicine shows tubulin binding, anti inflammatory activity and antimitotic effect similar to those of colchicine while doses 3 to 10 times higher than colchicine were well tolerated by different experimental animals. This preparation therefore carries the potential to replace colchicine as standard therapy for FMF and possibly also for other diseases now treated by colchicine.
KeywordsLiver Fibrosis Primary Biliary Cirrhosis Familial Mediterranean Fever Acute Gouty Arthritis Saline Treated Control Group
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- 1.S. E. Golfenger, Colchicine for Familial Mediterranean Fever, New Eng J Med. 287: 1302–1306 (1972).Google Scholar
- 6.H. G. Capraro and A. Brossi, “Tropolonic Colchicine Alkaloids” in vol 23 of “The Alkaloids” (ed Brossi A.I, Academic Press, New York, pp 1–70 (1984).Google Scholar
- 7.I. Kedar, M. Ravid, E. Sohar and J. Gafni, Colchicine inhibition of casein induced amyloidosis in mice, Isr J Med Sci. 19:787–789 (1974).Google Scholar
- 8.P. Kerekes, P. N. Sharma, A. Brossi, C. F. Chignell and F. R. Quium, Synthesis and biological effects of novel thiocolchicines. 3. evaluation of n-acyldeacetylthiocolchicine, n-(alkoxycarbonyl) deacetylthiocolchicines, and o-ethyldemethylthiocolchicines. New synthesis of thiocolchicine and antileukemic effects of 2-demethyl and 3-demethylthiocolchicine, J of Med Chem. 28:1204–1208 (1985).CrossRefGoogle Scholar
- 9.A. Brossi, P. N. Sharman, L. Atwell, A. E. Jacobson, M. A. Iorio, M. Molinari and C. F. Chignell. ibid. 1365-1369 (1983).Google Scholar
- 10.I. Kedar, M. Greenwald and M. Ravid, Colchicine Inhibition of the first phase of amyloid synthasis in experimental animals, Brit J Exp Pathol. 57:686–689 (1976).Google Scholar
- 12.L. Wilson, J. R. Bamburg and S. B. Mizel, Interaction of drugs with microtubule proteins, Fed Proc. 33:158–166.Google Scholar
- 13.S. E. Malawista, The action of Colchicine in acute gouty arthritis, Rheum. 8:750–756 (1965).Google Scholar
- 14.Vi-han-change. Mechanism of action of colchicine effects of colchicine and its analogs on phagocytosis and chemotaxis in vitro, Pharmacol exp ther. 194:159–164 (1975).Google Scholar