Histone deacetylase Apicidin

Histones of Plasmodium falciparum represent a new target for antimalarials. Apicidin [Cyclo (N-O-methyl-L-tryptophanyl-L-isoleucinyl-D-pipecolinyl-L-2-amino-oxodecanoyl] is a potent, broad spectrum antiprotozoal agent. The target of apicidin is Histone deacetylases HDA (Darkin Rattray et al., 1996), evidenced as hyperacetylation of histones in treated parasites. 

Darkin-Rattray SJ, Gurnett AM, Myers RW, Dulski PM, Crumley TM, Allocco JJ, Cannova C, Meinke PT, Colletti SL, Bednarek MA, Singh SB, Goetz MA, Dombrowski AW, Polishook JD, Schmatz DM (1996) Apicidin A novel antiprotozoal agent that inhibits parasite histone deacetylase. Proc Natl Acad Sci USA 93(23) 13143-13147... 

Kwon SH, Ahn SH, Kim YK, Bae GU, Yoon JW, Hong S, Lee HY, Lee YW, Lee HW, Han JW. (2002) Apicidin, a histone deacetylase inhibitor, induces apoptosis and Fas/Fas ligand expression in human acute promyelocytic leukemia cells. J Biol Chem 111 2073-2080. 

Colletti SL, Myers RW, Darkin-Rattray SJ, Gumett AM, Dnlski PM, Galuska S, Allocco JJ, Ayer MB, Li C, Lim J, Crumley TM, Cannova C, Schmatz DM, Wyvratt MJ, Fisher MH, Meinke PT. (2001) Broad spectrum antiprotozoal agents that inhibit histone deacetylase Strnctnre-activity relationships of apicidin. Part 2. Bioorg Med Chem Lett 11 113-117. 

Singh SB, Zink DL, Liesch JM, Mosley RT, Dombrowski AW, Bills GF, Darkin-Rattray SJ, Schmatz DM, Goetz MA. (2002) Structure and chemistry of apicidins, a class of novel cychc tetrapeptides without a terminal a-keto epoxide as inhibitors of histone deacetylase with potent antiprotozoal activities. J Org Chem 67 815-825. 

Kim MS, Son MW, Kim WB, In Park Y, Moon A. Apicidin, an inhibitor of histone deacetylase, prevents H-ras-induced invasive phenotype. Cancer Lett. 2000 157 23-30. 

Darkin-Rattray SJ et al (1996) Apicidin a novel antiprotozoal agent that inhibits parasite histone deacetylase. Proc Natl Acad Sci USA 93(23) 13143-13147... 

Kwon, S. Hong, H.Y. Lee, Y.W. Lee, H.W. Lee, Apicidin, a histone deacetylase inhibitor, inhibits proliferation of tumor cells via... 

K. W. Kim, W.B. Kim, S. Hong, Apicidin is a histone deacetylase inhibitor with anti-invasive and anti-angiogenic potentials, Biochem. Biophys. Res. Commun. 2004, 315, 964-970. 

Apicidin 38a,b Fusarium paUidoroseum [115] Antiprotozoal agent that inhibits parasite histone deacetylase [116] Mou and Singh [117]... 

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