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Synthesis and Immunosuppressive Activity of Novel Succinylacetone Analogues  

Kim, Taek-Hyeon (Department of Applied Chemistry, College of Engineering, Chonnam National University)
Oh, Dong-Ryun (Department of Applied Chemistry, College of Engineering, Chonnam National University)
Na, Hee-Sam (Department of Microbiology, Chonnam National University Medical School)
Lee, Hyun-Chul (Department of Microbiology, Chonnam National University Medical School)
Publication Information
Archives of Pharmacal Research / v.26, no.3, 2003 , pp. 192-196 More about this Journal
Abstract
This study describes the synthesis of novel enol esters (3) and triketones (4) as analogues of succinylacetone (SA) (Ed- this abbreviation is introduced here based on your use of it in the body of the paper) and the evaluation on the mouse allogeneic mixed lymphocyte reaction (MLR) and the murine model of antigen-induced paw edema formation for immunosuppressive activity. Enol esters (3a-f) were about 2-4 fold more potent than SA in in vitro activity.
Keywords
Immunosuppressive activity; Succinylacetone; Alkylacyloxy enol esters; Mixed lymphocyte reaction (MLR); Antigen-induced; Paw edema formation;
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1 Fidler, J. M., Chang, T. G., Bauer, R., Young, J. D., and Vitt, C. R., Suppression of graft-versus-host disease by succinylacetone in a rat allogeneic bone marrow transplantation model. Transplantation, 55, 367-373 (1993)   DOI   PUBMED   ScienceOn
2 Hess, R. A., Tschudy, D. P., and Blaese, R. M., Immunosuppression by succinylacetone: II. prevention of graft-vs.-host disease. J. Immunol., 139, 2845-2849 (1987)   PUBMED
3 Tang, Q. and Sen, S. E., Carbomethoxypropionyl cyanide: a regioselective C-alkylation reagent for the preparation of $\beta$-dicarbonyl compounds. Tetrahedron Lett., 39, 2249-2252 (1998)   DOI   ScienceOn
4 Borel, J. F., History of cyclosporin A and its significance in immunology. In cyclosporin A, Borel, J. F., Ed., Elsevier Biochemical Press: Amsterdam, 1982, pp 5-17
5 Elison, G. B. and Hitchings G. H., Azathioprine. Handb. Exp. Pharmacol., 38, 404-425 (1975)
6 Shaw, L. M., Kaplan, B. and Kaufman, D., Toxic effects of immunosuppressive drugs: mechanism and strategies for controlling them. Clin. Chem., 42, 1316-1321 (1996)   PUBMED
7 O'Keefe, S. J. and O'Neill, E. A., Cyclosporin A and FK506: immunosuppression, inhibition of transcription and the role of calcineurin. Perspect. Drug Discovery Des., 2, 85-102 (1994)   DOI
8 Tanaka, H., Kuroda, A., Marusawa, H., Hatanaka, H., Kino, T., Goto, T., Hashimoto, M., and Taga, T., Structure of FK506: a novel immunosuppressant (Ed- confirm the singular) isolated from Streptomyces. J. Am. Chem. Soc., 109, 5031-5033 (1987)   DOI
9 Akhrem, A. A., Lakhvich, F. A., Budai, S. I., Khlebnicova, T. S., and Petrusevich, I. I., A new simple synthesis of 2-acylcyclo-hexane-1,3-diones. Synthesis, 925-927 (1978)
10 Di Pierro, F., dAtri, G., Marcucci, F., and Leoni, F., Use of type I and type IV hypersensitivity responses to define the immuno-pharmacological profile of drugs. J. Pharmacol. Toxicol. Methods, 37, 91-96 (1997)   DOI   ScienceOn
11 Nitecki, D. E., Moreland, M., Aldwin, L., Levenson, C. H., Braude, I. and Mark, D. F., Preparation of succinylacetone derivatives and analogs as immunosuppressive agents. WO 9000049 (1990)
12 Montes, I. F. and Burger, U., The cyanide catalyzed isomerisation of enol esters derived from cyclic 1,3-diketones. Tetrahedron Lett., 37, 1007-1010 (1996)   DOI   ScienceOn
13 Tschudy, D. P., Hess, R., Frykholm, B., and Blaese, R. M., Immunosuppressive activity of succinylacetone. J. Lab. Clin. Med., 99, 526-532 (1981)
14 Meo, T., The MLR test in the mouse. In immunological methods, Lefkovits, I., Pernis, B., Eds., Academic Press: New York, 1979, pp 227-239
15 Kawai, M., Lane, B. C., Hsieh, G. C., Mollison, K. W., Carter, G. W., and Luly, J. R., FEBS. Lett., 316, 107 (1993)   DOI   ScienceOn
16 Perico, N. and Remuzzi, G., Prevention of transplant rejection current treatment guidelines and future developments. Drugs, 54, 533-570 (1997)   DOI   ScienceOn
17 Sanders, S. and Harisdangkul, V. Leflunomide for the treatment of rheumatoid arthritis and autoimmunity. Am. J. Med. Sci., 323, 190-193 (2002)   DOI   ScienceOn
18 Silverman, R. B., The organic chemistry of drug design and drug action. Academic Press, New York, pp. 19-24 (1992)
19 Skolik, S. A., Palestine, A. G., Blaese, R. M. Nussenblatt, R. B., and Hess, R. A., Treatment of experimental autoimmune uveitis in the rat with systemic succinylacetone. Clin. Immunol. Immunopathol. 49, 63-71 (1988)   DOI   ScienceOn
20 Lindblad, B., Lindstedt, S., and Steen, G., On the enzyme defects in hereditary tyrosinemia. Proc. Natl. Acad. Sci. USA, 74, 4641-4645 (1977)   DOI   ScienceOn