Discovery and mechanism of natural products as modulators of histone acetylation

Current Drug Targets

Volumn 13, Issue 8, 2012, Pages 1029-1047

  Salvador, Lilibeth A ^a   Luesch, Hendrik ^a  

^a UNIVERSITY OF FLORIDA   (United States)

Author keywords

Histone acetylation; Histone acetyltransferases; Histone deacetylases; Natural products; Secondary metabolites

Indexed keywords

ANACARDIC ACID; APICIDIN; AZACITIDINE; AZUMAMIDE A; AZUMAMIDE B; AZUMAMIDE C; AZUMAMIDE E; CURCUMIN; DEPUDECIN; FR 235222; FR 901375; GARCINOL; GUTTIFERONE A; GUTTIFERONES E; HISTONE DEACETYLASE INHIBITOR; ISOGARCINOL; LARGAZOLE; NATURAL PRODUCT; NEMOROSONE; POLYPHENOL; PSAMMAPLIN A; ROMIDEPSIN; SPIRUCHOSTATIN A; SPIRUCHOSTATIN B; TETRAPEPTIDE; TRAPOXIN A; TRAPOXIN B; TRICHOSTATIN A; UNCLASSIFIED DRUG; UNINDEXED DRUG; VORINOSTAT;

ARTICLE; DRUG BINDING; DRUG CYTOTOXICITY; DRUG DEVELOPMENT; DRUG MECHANISM; DRUG STRUCTURE; DRUG TARGETING; EPIGENETICS; HISTONE ACETYLATION; HUMAN; MYELODYSPLASTIC SYNDROME; NONHUMAN; PHARMACOPHORE; PROTEIN MODIFICATION; PROTEIN PROCESSING; STRUCTURE ACTIVITY RELATION; T CELL LYMPHOMA;

ACETYLATION; BIOLOGICAL AGENTS; DRUG DISCOVERY; HISTONES; PROTEIN PROCESSING, POST-TRANSLATIONAL;

EID: 84863548736     PISSN: 13894501     EISSN: 18735592     Source Type: Journal    
DOI: 10.2174/138945012802008973     Document Type: Article

References (172)

1. Ortholand J, Ganesan A. Natural products and combinatorial chemistry: back to the future. Curr Opin Chem Biol 2004; 8: 271-80.
2. Koehn FE, Carter GT. The evolving role of natural products in drug discovery. Nat Rev Drug Discov 2005; 4: 206-20.
3. Newman DJ, Cragg GM. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 2012; 75: 311-35.
4. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000; 100: 57-70.
5. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell 2011; 144: 646-74.
6. Jones PA, Baylin SB. The epigenomics of cancer. Cell 2007; 128: 683-92.
7. Sharma S, Kelly TK, Jones PA. Epigenetics in cancer. Carcinogenesis 2010; 31: 27-36.
8. Li B, Carey M, Workman JL. The role of chromatin during transcription. Cell 2007; 128: 707-19.
9. Luger K, Mader AW, Richmond RK, Sargent DF, Richmond TJ. Crystal structure of the nucleosome core particle at 2.8Å resolution. Nature 1997; 389: 251-60.
10. Kornberg RD, Lorch Y. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 1999; 98: 285-94.
11. Kouzarides T. Chromatin modifications and their function. Cell 2007; 128: 693-705.
12. Lee J, Smith E, Shilatifard A. The language of histone crosstalk. Cell 2010; 142: 682-5.
13. Oliver SS, Denu JM. Dynamic interplay between histone H3 modifications and protein interpreters: Emerging evidence for a "histone language". Chem Bio Chem 2011; 12: 299-307.
14. Choudhary C, Kumar C, Gnad F, et al. Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science 2009; 325: 834-40.
15. Zhao S, Xu W, Wenqing J, et al. Regulation of cellular metabolism by protein lysine acetylation. Science 2010; 327: 1000-4.
16. Gregoretti IV, Lee Y, Goodson HV. Molecular evolution of the histone deacetylase family: Functional implications of phylogenetic analysis. J Mol Biol 2004; 338: 17-31.
17. de Ruijter AJ, van Gennip AH, Caron HN, Kemp S, van Kuilenburg AB. Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem J 2003; 370: 737-49.
18. Ficner R. Novel structural insights into class I and II histone deacetylases. Curr Top Med Chem 2009; 9: 235-240.
19. Lahm A, Paolini C, Pallaoro M, et al. Unraveling the hidden catalytic activity of vertebrate class IIa histone deacetylases. Proc Natl Acad Sci USA 2007; 104: 17335-40.
20. Somoza JR, Skene RJ, Katz BA, et al. Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. Structure 2004; 12: 1325-34.
21. Vannini A, Volpari C, Filocamo G, et al. Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proc Natl Acad Sci USA 2004; 101: 15064-9.
22. Schuetz A, Min J, Allali-Hassani A, et al. Human HDAC7 harbors a class IIa histone deacetylase-specific zinc binding motif and cryptic deacetylase activity. J Biol Chem 2008; 283: 11355-63.
23. Cole KE, Dowling DP, Boone MA, Phillips AJ, Christianson DW. Structural basis of the antiproliferative activity of largazole, a depsipeptide inhibitor of the histone deacetylases. J Am Chem Soc 2011; 133: 12474-7.
24. Dowling DP, Gantt SL, Gattis SG, Fierke CA, Christianson DW. Structural studies of human histone deacetylase 8 and its sitespecific variants complexed with substrate and inhibitors. Biochemistry 2008; 47: 13554-63.
25. Bolden J, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors. Nat Rev Drug Dis 2006; 5: 769-84.
26. Sievers F, Wilm A, Dineen DG, et al. Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega. Mol Syst Biol 2011; 7: 539.
27. Edgar RC, Sjolander K. SATCHMO: Sequence alignment and tree construction using Hidden Markov Models. Bioinformatics 2003; 19: 1404-11.
28. Smith BC, Denu JM. Chemical mechanisms of histone lysine and arginine modifications. Biochim Biophys Acta 2009; 1789: 45-57.
29. Hodawadekar SC, Marmorstein R. Chemistry of acetyl transfer by histone modifying enzymes: structure, mechanism and implications for effector design. Oncogene 2007; 26: 5528-40.
30. Berndsen CE, Albaugh BN, Tan S, Denu JM. Catalytic mechanism of a MYST family histone acetyltransferase. Biochemistry 2007; 46: 623-9.
31. Tanner KG, Trievel RC, Kuoi M, et al. Catalytic mechanism and function of invariant glutamic acid 173 from the histone acetyltransferase GCN5 transcriptional coactivator. J Biol Chem 1999; 274: 18157-60.
32. Lin Y, Fletcher CM, Zhou J, Allis CD, Wagner G. Solution structure of the catalytic domain of GCN5 histone acetyltransferase bound to coenzyme A. Nature 1999; 400: 86-9.
33. Liu X, Wang L, Zhao K, et al. The structural basis of protein acetylation by the p300/CBP transcriptional coactivator. Nature 2008; 451: 846-50.
34. Liang G, Lin JCY, Wei V, et al. Distinct localization of histone H3 acetylation and H3-K4 methylation to the transcription start sites in the human genome. Proc Natl Acad Sci USA 2004; 101: 7357-62.
35. Fraga MF, Ballestar E, Villar-Garea A, et al. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer. Nature Genet 2005; 37: 391-400.
36. Seligson DB, Horvath S, Shi T, et al. Global histone modification patterns predict risk of prostate cancer recurrence. Nature 2005; 435: 1262-6.
37. Nakagawa M, Oda Y, Eguchi T, et al. Expression profile of class I histone deacetylases in human cancer tissues. Oncol Rep 2007; 18: 769-74.
38. Halkidou K, Gaughan L, Cook S, Leung HY, Neal DE, Robson CN. Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer. Prostate 2004; 59: 177-89.
39. Song J, Noh JH, Lee JH, et al. Increased expression of histone deacetylase 2 is found in human gastric cancer. Acta Path Micro Im 2005; 113: 264-8.
40. Fry DG, Hurlin PJ, Maher VM, McCormick JJ. Transformation of diploid human fibroblasts by transfection with the v-sis, PDGF2/csis, or T24 H-ras genes. Mutat Res 1988; 199: 341-51.
41. Wegener D, Wirsching F, Riester D, Schwienhorst A. A fluorogenic histone deacetylase assay well suited for high-throughput activity screening. Chem Biol 2003; 10: 61-68.
42. Yoshida M, Kijima M, Akita M, Beppu T. Potent and specific inhibition of mammalian histone deacetylase both in vivo and in vitro by trichostatin A. J Biol Chem 1990; 265: 17174-9.
43. Kijima M, Yoshida M, Sugita K, Horinouchi S, Beppu T. Trapoxin, an antitumor cyclic tetrapeptide, is an irreversible inhibitor of mammalian histone deacetylase. J Biol Chem 1993; 268: 22429-35.
44. Finnin MS, Donigian JR, Cohen A, et al. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors. Nature 1999; 401: 188-93.
45. Taunton J, Collins JL, Schreiber SL. Synthesis of natural and modified trapoxins, useful reagents for exploring histone deacetylase function. J Am Chem Soc 1996; 118: 10412-22.
46. Nakajima H, Kim YB, Terano H, Yoshida M, Horinouchi S. FR901228, a potent antitumor antibiotic, is a novel histone deacetylase inhibitor. Expt Cell Res 1998; 241: 126-33.
47. Uekia M, Teruya T, Nie L, Usamib R, Yoshida M, Osada H. New trichostatin derivative, trichostatin RK, from Streptomyces sp. RK98-A74. J Antibiot 2001; 54: 1093-5.
48. McCulloch MWB, Coombs GS, Banerjee N, et al. Psammaplin A as a general activator of cell-based signaling assays via HDAC inhibition and studies on some bromotyrosine derivatives. Bioorg Med Chem 2009; 17: 2189-98.
49. Wilson AJ, Byun D, Popova N, et al. Histone deacetylase 3 (HDAC3) and other class I HDACs regulate colon cell maturation and p21 expression and are deregulated in human colon cancer. J Biol Chem 2006; 281: 13548-58.
50. Balasubramanyam K, Swaminathan V, Ranganathan A, Kundu TK. Small molecule modulators of histone acetyltransferase p300. J Biol Chem 2003; 278: 19134-40.
51. Berndsen CE, Denu JM. Assays for mechanistic investigations of protein/histone acetyltransferases. Methods 2005; 36: 321-31.
52. Paris M, Porcelloni M, Binaschi M, Fattori D. Histone deacetylase inhibitors: From bench to clinic. J Med Chem 2008; 51: 1505-29.
53. KrennHrubec K, Marshall BL, Hedglin M, Verdin E, Ulrich SM. Design and evaluation of 'linkerless' hydroxamic acids as selective HDAC8 inhibitors. Bioorg Med Chem Lett 2007; 17: 2874-78.
54. Hong J, Luesch H. Largazole: From discovery to broad-spectrum therapy. Nat Prod Rep 2012; 29: 449-56.
55. Dashwood RH, Myzak MC, Ho E. Dietary HDAC inhibitors: time to rethink weak ligands in cancer chemoprevention? Carcinogenesis 2006; 27: 344-9.
56. Cousens LS, Gallwitz D, Alberts BM. Different accessibilities in chromatin to histone acetylase. J Biol Chem 1979; 254: 1716-23.
57. Newkirk TL, Bowers AA, Williams RM. Discovery, biological activity, synthesis and potential therapeutic utility of naturally occurring histone deacetylase inhibitors. Nat Prod Rep 2009; 26: 1293-320.
58. Tsuis N, Kobayashi M, Nagashima K, Wakisaka Y, Koizumi K. A new antifungal antibiotic, trichostatin. J Antibiot 1976; 29: 1-6.
59. Yoshida M, Nomura S, Beppu T. Effects of trichostatins on differentiation of murine erythroleukemia cells. Cancer Res 1987; 47: 3688-91.
60. Hayakawa Y, Nakai M, Furihata K, Shin-ya K, Seto H. Trichostatin D, a new inducer of phenotypic reversion in transformed cells. J Antibiot 2000; 53: 179-83.
61. Morioka H, Ishihara M, Takezawa M, et al. A new differentiation inducer of Friend leukemia cells, trichostatic acid. Agric Biol Chem 1985; 49: 1365-70.
62. Tsuji N, Kobayashi M. Trichostatin C, a glucopyranosyl hydroxamate. J Antibiot 1978; 31: 940-4.
63. Ueda J, Hwang J, Maeda S, et al. JBIR-17, a novel trichostatin analog from Streptomyces sp. 26634. J Antibiot 2009; 62: 283-5.
64. Matsumoto M, Matsutani S, Sugita K, et al. Depudecin: A novel compound inducing the flat phenotype of NIH3T3 cells doubly transformed by ras-and src-oncogene, produced by Alternaria brassicicola. J Antibiot 1992; 45: 879-5.
65. Tanaka M, Fujimori T, Nabeta K. Biosynthesis of depudecin, a metabolite of Nimbya scirpicola. Biosci Biotechnol Biochem 2000; 64: 244-7.
66. Quinoa E, Crews P. Phenolic constituents of Psammaplysilla. Tetrahedron Lett 1987; 28: 3229-32.
67. Jimenez C, Crews P. Novel marine sponge derived amino acids 13. Additional psammaplin derivatives from Psammaplysilla purpurea. Tetrahedron 1991; 47: 2097-102.
68. Pham NB, Butler MS, Quinn RJ. Isolation of psammaplin A 11'-sulfate and bisaprasin 11'-sulfate from the marine sponge Aplysinella rhax. J Nat Prod 2000; 63: 393-5.
69. Shin J, Lee H, Seo Y, Rho J, Cho KW, Paul VJ. New bromotyrosine metabolites from the sponge Aplysinella rhax. Tetrahedron 2000; 56: 9071-9077.
70. Pina IC, Gautschi JT, Wang G, et al. Psammaplins from the sponge Pseudoceratina purpurea: Inhibition of both histone deacetylase and DNA methyltransferase. J Org Chem 2003; 68: 3866-73.
71. Kim DH, Shin J, Kwon HJ. Psammaplin A is a natural prodrug that inhibits class I histone deacetylase. Exp Mol Med 2007; 39: 47-55.
72. Marfey P. Determination of D-amino acids. II. Use of a bifunctional reagent, 1,5-difluoro-2,4-dinitrobenzene. Carlsberg Res Commun 1984; 49: 591-6.
73. Fujii K, Ikai Y, Oka H, Suzuki M, Harada K. A nonempirical method using LC/MS for determination of the absolute configuration of constituent amino acids in a peptide: combination of Marfey's method with mass spectrometry and its practical application. Anal Chem 1997; 69: 5146-51.
74. Dale JA, Mosher HS. Nuclear magnetic resonance enantiomer reagents. Configurational correlations via nuclear magnetic resonance chemical shifts of diastereomeric mandelate, Omethylmandelate, and α-methoxy-α-trifluoromethylphenylacetate (MTPA) esters. J Am Chem Soc 1973; 95: 512-9.
75. Itazaki H, Nagashima K, Sugita K, et al. Isolation and structural elucidation of new cyclotetrapeptides, trapoxins A and B, having detransformation activities as antitumor agents. J Antibiot 1990; 43: 1524-32.
76. Rasmussen JB, Scheffer RP. Isolation and biological activities of four selective toxins from Helminthosporium carbonum. Plant Physiol 1988; 86: 187-91.
77. Closse A, Huguenin R. Isolierung und Strukturaufklärung von Chlamydocin. Helv Chim Acta 1974; 57: 533-45.
78. Umehara K, Nakahara K, Kiyoto S, et al. Studies on WF-3161, a new antitumor antibiotic. J Antibiot 1983; 36: 478-83.
79. Hirota A, Suzuki A, Suzuki H, Tamura S. Isolation and biological activity of Cyl-2, a metabolite of Cylindrocladium scoparium. Agric Biol Chem 1973; 37: 643-47.
80. Gu W, Cueto M, Jensen PR, Fenical W, Silverman RB. Microsporins A and B: new histone deacetylase inhibitors from the marine-derived fungus Microsporum cf. gypseum and the solidphase synthesis of microsporin A. Tetrahedron 2007; 63: 6535-41.
81. Singh SB, Zink DL, Polishook JD, et al. Apicidins: novel cyclic tetrapeptides as coccidiostats and antimalarial agents from Fusarium pallidoroseum. Tetrahedron Lett 1996; 37: 8077-80.
82. Singh SB, Zink DL, Liesch JM, et al. Structure, histone deacetylase, and antiprotozoal activities of apicidins B and C, congeners of apicidin with proline and valine substitutions. Org Lett 2001; 3: 2815-8.
83. Singh SB, Zink DL, Liesch JM, et al. Structure and chemistry of apicidins, a class of novel cyclic tetrapeptides without a terminal α-keto epoxide as inhibitors of histone deacetylase with potent antiprotozoal activities. J Org Chem 2002; 67: 815-25.
84. Mori H, Urano Y, Abe F, et al. FR235222, a fungal metabolite, is a novel immunosuppressant that inhibits mammalian histone deacetylase (HDAC). I. Taxonomy, fermentation, isolation and biological activities. J Antibiot 2003; 56: 72-9.
85. Mori H, Abe F, Furukawa S, et al. FR235222, a fungal metabolite, is a novel immunosuppressant that inhibits mammalian histone deacetylase (HDAC). II. Biological activities in animal models. J Antibiot 2003; 56: 80-6.
86. Mori H, Urano Y, Kinoshita T, Yoshimura S, Takase S, Hino M. FR235222, a fungal metabolite, is a novel immunosuppressant that inhibits mammalian histone deacetylase. III. Structure determination. J Antibiot 2003; 56: 181-5.
87. Gomez-Paloma L, Bruno I, Cini E, et al. Design and synthesis of cyclopeptide analogs of the potent histone deacetylase inhibitor FR235222. Chem Med Chem 2007; 2: 1511-9.
88. Sasamura S, Sakamoto K, Takagaki S, et al. AS1387392, a novel immunosuppressive cyclic tetrapeptide compound with inhibitory activity against mammalian histone deacetylase. J Antibiot 2010; 63: 633-36.
89. Nakao Y, Yoshida S, Matsunaga S, et al. Azumamides A-E: Histone deacetylase inhibitory cyclic tetrapeptides from the marine sponge Mycale izuensis. Angew Chem Int Ed 2006; 45: 7553-7.
90. Kwan JC, Luesch H. Weapons in disguise-activating mechanisms and protecting group chemistry in Nature. Chem Eur J 2010; 16: 13020-9.
91. Ueda H, Nakajima H, Hori Y, et al. FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. I. Taxonomy, fermentation, isolation, physico-chemical and biological properties, and antitumor activity. J Antibiot 1994; 47: 301-10.
92. Shigematsu N, Ueda H, Takase S, Tanaka H. FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. II. Structure determination. J Antibiot 1994; 47: 311-4.
93. Furumai R, Matsuyama A, Kobashi N, et al. FK228 (Depsipeptide) as a natural prodrug that inhibits class I histone deacetylases. Cancer Res 2002; 62: 4916-21.
94. Masuoka Y, Nagai A, Shin-ya K, et al. Spiruchostatins A and B, novel gene expression-enhancing substances produced by Pseudomonas sp. Tetrahedron Lett 2001; 42: 41-4.
95. Chen Y, Gambs C, Abe Y, Wentworth PJ, Janda KD. Total synthesis of the depsipeptide FR-901375. J Org Chem 2003; 68: 8902-5.
96. Taori K, Paul VJ, Luesch H. Structure and activity of largazole, a potent antiproliferative agent from the Floridian marine cyanobacterium Symploca sp. J Am Chem Soc 2008; 130: 1806-7.
97. Ying Y, Taori K, Kim H, Hong J, Luesch H. Total synthesis and molecular target of largazole, a histone deacetylase inhibitor. J Am Chem Soc 2008; 130: 8455-9.
98. Balasubramanyam K, Varier RA, Altaf M, et al. Curcumin, a novel p300/CREB-binding protein-specific inhibitor of acetyltransferase, represses the acetylation of histone/nonhistone proteins and histone acetyltransferase-dependent chromatin transcription. J Biol Chem 2004; 279: 51163-71.
99. Choi K, Jung MG, Lee YH, et al. Epigallocatechin-3-gallate, a histone acetyltransferase inhibitor, inhibits EBV-induced B lymphocyte transformation via suppression of RelA acetylation. Cancer Research 2009; 69: 583-92.
100. Ghizzoni M, Boltjes A, Graaf C, Haisma HJ, Dekker FJ. Improved inhibition of the histone acetyltransferase PCAF by an anacardic acid derivative. Bioorg Med Chem 2010; 18: 5826-34.
101. Balasubramanyam K, Altaf M, Varier RA, et al. Polyisoprenylated benzophenone, garcinol, a natural histone acetyltransferase inhibitor, represses chromatin transcription and alters global gene expression. J Biol Chem 2004; 279: 33716-26.
102. Dal Piaz F, Tosco A, Eletto D, et al. The identification of a novel natural activator of p300 histone acetyltranferase provides new insights into the modulation mechanism of this enzyme. ChemBio-Chem 2010; 11: 818-27.
103. Arif M, Pradhan SK, Thanuja GK, et al. Mechanism of p300 specific histone acetyltransferase inhibition by small molecules. J Med Chem 2009; 52: 267-77.
104. Wang D, Helquist P, Wiech NL, Wiest O. Toward selective histone deacetylase inhibitor design: Homology modeling, docking studies, and molecular dynamics simulations of human class I histone deacetylases. J Med Chem 2005; 48: 6936-47.
105. Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010; 31: 455-61.
106. Marks PA, Breslow R. Dimethyl sulfoxide to vorinostat: development of this histone deacetylase inhibitor as an anticancer drug. Nat Biotechnol 2007; 25: 84-90.
107. Kranz M, Murray PJ, Taylor S, Upton RJ, Clegg W, Elsegood MR. Solution, solid phase and computational structures of apicidin and its backbone-reduced analogs. J Pept Sci 2006; 12: 383-8.
108. Meinke PT, Colletti SL, Ayer MB, et al. Synthesis of side chain modified apicidin derivatives: potent mechanism-based histone deacetylase inhibitors. Tetrahedron Lett 2000; 41: 7831-5.
109. Colletti SL, Li C, Fisher MH, Wyvratt MJ, Meinke PT. Tryptophan-replacement and indole-modified apicidins: synthesis of potent and selective antiprotozoal agents. Tetrahedron Lett 2000; 41: 7825-9.
110. Colletti SL, Myers RW, Darkin-Rattray SJ, et al. Broad spectrum antiprotozoal agents that inhibit histone deacetylase: structureactivity relationships of apicidin. Part 1. Bioorg Med Chem Lett 2001; 11: 107-11.
111. Colletti SL, Myers RW, Darkin-Rattray SJ, et al. Broad spectrum antiprotozoal agents that inhibit histone deacetylase: structure-activity relationships of apicidin. Part 2. Bioorg Med Chem Lett 2001; 11: 113-7.
112. Rodriquez M, Terracciano S, Cini E, et al. Total synthesis, NMR solution structure, and binding model of the potent histone deacetylase inhibitor FR235222. Angew Chem Int Ed 2006; 45: 423-7.
113. Singh EK, Ravula S, Pan CM, et al. Synthesis and biological evaluation of histone deacetylase inhibitors that are based on FR235222: a cyclic tetrapeptide scaffold. Bioorg Med Chem Lett 2008; 18: 2549-54.
114. Di Micco S, Terracciano S, Bruno I, et al. Molecular modeling studies toward the structural optimization of new cyclopeptide-based HDAC inhibitors modeled on the natural product FR235222. Bioorg Med Chem 2008; 16: 8635-42.
115. Maulucci N, Chini MG, Di Micco SG, et al. Molecular insights into azumamide E histone deacetylases inhibitory activity. J Am Chem Soc 2007; 129: 3007-12.
116. Bowers A, West N, Taunton J, Schreiber SL, Bradner JE, Williams RM. Total synthesis and biological mode of action of largazole: A potent class I histone deacetylase inhibitor. J Am Chem Soc 2008; 130: 11219-22.
117. Nasveschuk CG, Ungermannova D, Liu X, Phillips AJ. A concise total synthesis of largazole, solution structure, and some preliminary structure activity relationships. Org Lett 2008; 10: 3595-8.
118. Seiser T, Kamena F, Cramer N. Synthesis and biological activity of largazole and derivatives. Angew Chem Int Ed 2008; 47: 6483-5.
119. Numajiri Y, Takahashi T, Takagi M, Shin-ya K, Doi T. Total synthesis of largazole and its biological evaluation. Synlett 2008; 16: 2483-6.
120. Ghosh AK, Kulkarni S. Enantioselective total synthesis of (+)-largazole, a potent inhibitor of histone deacetylase. Org Lett 2008; 10: 3907-9.
121. Wang B, Huang PH, Chen CS, Forsyth CJ. Total syntheses of the histone deacetylase inhibitors largazole and 2-epi-largazole: application of N-heterocyclic carbene mediated acylations in complex molecule synthesis. J Org Chem 2011; 76: 1140-50.
122. Ying Y, Liu Y, Byeon SR, Kim H, Luesch H, Hong J. Synthesis and activity of largazole analogues with linker and macrocycle modification. Org Lett 2008; 10: 4021-4.
123. Chen F, Gao AH, Li J, Nan FJ. Synthesis and biological evaluation of C7-demethyl largazole analogues. Chem Med Chem 2009; 4: 1269-72.
124. Bowers AA, West N, Newkirk TL, et al. Synthesis and histone deacetylase inhibitory activity of largazole analogs: alteration of the zinc-binding domain and macrocyclic scaffold. Org Lett 2009; 11: 1301-4.
125. Bowers AA, Greshock TJ, West N, et al. Synthesis and conformation-activity relationships of the peptide isosteres of FK228 and largazole. J Am Chem Soc 2009; 131: 2900-5.
126. Zeng X, Yin B, Hu Z, et al. Total synthesis and biological evaluation of largazole and derivatives with promising selectivity for cancers cells. Org Lett 2010; 12: 1368-71.
127. Liu Y, Salvador LA, Byeon S, et al. Anticolon cancer activity of largazole, a marine-derived tunable histone deacetylase inhibitor. J Pharmacol Exp Ther 2010; 335: 351-61.
128. Shimada J, Kwon HJ, Sawamura M, Schreiber S. Synthesis and cellular characterization of the detransformation agent, (-)-depudecin. Chem Biol 1995; 2: 517-25.
129. Taunton J, Hassig CA, Schreiber SL. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 1996; 272: 408-11.
130. Barlev NA, Liu L, Chehab NH, et al. Acetylation of p53 activates transcription through recruitment of coactivators/histone acetyltransferases. Mol Cell 2001; 8: 1243-54.
131. Wang YH, Tsay YG, Tan BC, Lo WY, Lee SC. Identification and characterization of a novel p300-mediated p53 acetylation site, lysine 305. J Biol Chem 2003; 278: 25568-76.
132. Tang Y, Zhao W, Chen Y, Zhao Y, Gu W. Acetylation is indispensable for p53 activation. Cell 2008; 133: 612-26.
133. Yamaguchi H, Woods NT, Piluso LG, et al. p53 acetylation is crucial for its transcription-independent proapoptotic functions. J Biol Chem 2009; 284: 11171-83.
134. Joubel A, Chalkley RJ, Medzihradszky KF, Hondermarck H, Burlingame AL. Identification of new p53 acetylation sites in COS-1 cells. Mol Cell Proteomics 2009; 8: 1167-73.
135. Zhao Y, Lu S, Wu L, et al. Acetylation of p53 at lysine 373/382 by the histone deacetylase inhibitor depsipeptide induces expression of p21Waf1/Cip1. Mol Cell Biol 2006; 26: 2782-90.
136. Quivy V, Van Lint C. Regulation at multiple levels of NF-κBmediated transactivation by protein acetylation. Biochem Pharmacol 2004; 68: 1221-9.
137. Chen LF, Williams SA, Mu Y, et al. NF-κB RelA phosphorylation regulates RelA acetylation. Mol Cell Biol 2005; 25: 7966-75.
138. Kiernan R, Brès V, Ng RW, et al. Post-activation turn-off of NF-κB-dependent transcription is regulated by acetylation of p65. J Biol Chem 2003; 278: 2758-66.
139. Deng WG, Wu KK. Regulation of inducible Nitric Oxide Synthase expression by p300 and p50 acetylation. J Immunol 2003; 171: 6581-8.
140. Deng WG, Zhu Y, Wu KK. Up-regulation of p300 binding and p50 acetylation in Tumor Necrosis Factor-α-induced Cyclooxygenase-2 promoter activation. J Biol Chem 2003; 278: 4770-7.
141. Zhang Y, Li N, Caron C, et al. HDAC-6 interacts with and deacetylates tubulin and microtubules in vivo. EMBO 2003; 22: 1168-79.
142. LeDizet M, Piperno G. Identification of an acetylation site of Chlamydomonas α-tubulin. Proc Natl Acad Sci USA 1987; 84: 5720-4.
143. Piperno G, LeDizet M, Chang XJ. Microtubules containing acetylated α-tubulin in mammalian cells in culture. J Cell Biol 1987; 104: 289-302.
144. Maruta H, Greet K, Rosenbaum JL. The acetylation of Alpha-Tubulin and its relationship to the assembly and disassembly of microtubules. J Cell Biol 1986; 103: 571-9.
145. Kawaguchi Y, Kovacs JJ, McLaurin A, Vance JM, Ito A, Yao TP. The deacetylase HDAC6 regulates aggresome formation and cell viability in response to misfolded protein stress. Cell 2003; 115: 727-38.
146. Hubbert C, Guardiola A, Shao R, et al. HDAC6 is a microtubuleassociated deacetylase. Nature 2002; 417: 455-8.
147. Zilberman Y, Ballestrem C, Carramusa L, Mazitschek R, Khochbin S, Bershadsky A. Regulation of microtubule dynamics by inhibition of the tubulin deacetylase HDAC6. J Cell Sci 2009; 122: 3531-41.
148. Yuan ZL, Guan YJ, Chatterjee D, Chin YE. Stat3 dimerization regulated by reversible acetylation of a single lysine residue. Science 2005; 307: 269-73.
149. Ray S, Lee C, Hou T, Boldogh I, Brasier AR. Requirement of histone deacetylase1 (HDAC1) in signal transducer and activator of transcription 3 (STAT3) nucleocytoplasmic distribution. Nucleic Acids Res 2008; 36: 4510-20.
150. Aoyagi S, Archer TK. Modulating molecular chaperone Hsp90 functions through reversible acetylation. Trends Cell Biol 2005; 15: 565-7.
151. Scroggins BT, Robzyk K, Wang D, et al. An acetylation site in the middle domain of Hsp90 regulates chaperone function. Mol Cell 2007; 25: 151-9.
152. Yang Y, Rao R, Shen J, et al. Role of acetylation and extracellular location of Heat Shock Protein 90A in tumor cell invasion. Cancer Res 2008; 68: 4833-42.
153. Vigushin DM, Ali S, Pace PE, et al. Trichostatin A is a histone deacetylase inhibitor with potent antitumor activity against breast cancer in vivo. Clin Cancer Res 2001; 7: 971-6.
154. Sanderson L, Taylor GW, Aboagye EO, et al. Plasma pharmacokinetics and metabolism of the histone deacetylase inhibitor trichostatin A after intraperitoneal administration to mice. Drug Met Disp 2004; 32: 1132-8.
155. Ahn MY, Na YJ, Lee J, Lee BM, Kim HS. Apicidin induces apoptosis via cytochrome c-mediated intrinsic pathway in human ovarian cancer cells. Biomol Ther 2009; 17: 17-24.
156. Ahn MY, Lee J, Na YJ, et al. Mechanism of apicidin-induced cell cycle arrest and apoptosis in Ishikawa human endometrial cancer cells. Chem Biol Interact 2009; 179: 169-77.
157. Ahn MY, Chung HY, Choi WS, Lee BM, Yoon S, Kim HS. Antitumor effect of apicidin on Ishikawa human endometrial cancer cells both in vitro and in vivo by blocking histone deacetylase 3 and 4. Int J Oncol 2010; 36: 125-31.
158. Shin BS, Chang HS, Park EH, et al. Pharmacokinetics of a novel histone deacetylase inhibitor, apicidin, in rats. Biopharm Drug Dispos 2006; 27: 69-75.
159. Noh JH, Song JH, Eun JW, et al. Systemic cell-cycle suppression by apicidin, a histone deacetylase inhibitor, in MDA-MB-435 cells. Int J Mol Med 2009; 24: 205-26.
160. Petrella A, D'Acunto CW, Rodriquez M, et al. Effects of FR235222, a novel HDAC inhibitor, in proliferation and apoptosis of human leukaemia cell lines: role of annexin A1. Eur J Cancer 2008; 44: 740-9.
161. D'Acunto CW, Fontanella B, Rodriquez M, Taddei M, Parente L, Petrella A. Histone deacetylase inhibitor FR235222 sensitizes human prostate adenocarcinoma cells to apoptosis through upregulation of annexin A1. Cancer Lett 2010; 295: 85-91.
162. D'Acunto CW, Carratu A, Rodriguez M, Taddei M, Parente L, Petrella A. LGP1, a histone deacetylase inhibitor analogue of FR235222, sensitizes promyelocytic leukemia U937 cells to TRAIL-mediated apoptosis. Anticancer Res 2010; 30: 887-94.
163. Ueda H, Manda T, Matsumoto S, et al. FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968 III. Antitumor activities on experimental tumors in mice. J Antibiot 1994; 47: 315-23.
164. Sasakawa Y, Naoe Y, Inoue T, et al. Effects of FK228, a novel histone deacetylase inhibitor, on tumor growth and expression of p21 and c-myc genes in vivo. Cancer Lett 2003; 195: 161-8.
165. Ito T, Ouchida M, Morimoto Y, et al. Significant growth suppression of synovial sarcomas by the histone deacetylase inhibitor FK228 in vitro and in vivo. Cancer Lett 2005; 224: 311-9.
166. Sasakawa Y, Naoe Y, Sogo N, et al. Marker genes to predict sensitivity to FK228, a histone deacetylase inhibitor. Biochem Pharmacol 2005; 69: 603-16.
167. Hoshino I, Hisahiro M, Akutsu Y, et al. Gene expression profiling induced by histone deacetylase inhibitor, FK228, in human esophageal squamous cancer cells. Oncol Rep 2007; 18: 585-92.
168. Chen G, Li A, Zhao M, et al. Proteomic analysis identifies protein targets responsible for depsipeptide sensitivity in tumor cells. J Proteome Res 2008; 7: 2733-42.
169. Lech-Maranda E, Robak E, Korycka A, Robak T. Depsipeptide (FK228) as a novel histone deacetylase inhibitor: mechanism of action and anticancer activity. Mini-Rev Med Chem 2007; 7: 1062-69.
170. Narita K, Kikuchi T, Watanabe K, et al. Total synthesis of the bicyclic depsipeptide HDAC inhibitors spiruchostatins A and B, 5″-epi-spiruchostatin B, FK228 (FR901228) and preliminary evaluation of their biological activity. Chem Eur J 2009; 15: 11174-86.
171. Crabb SJ, Howell M, Rogers H, et al. Characterisation of the in vitro activity of the depsipeptide histone deacetylase inhibitor spiruchostatin A. Biochem Pharmacol 2008; 76: 463-75.
172. Thaler F, Minucci S. Next generation histone deacetylase inhibitors: The answer to the search for optimized epigenetic therapies? Expert Opin Drug Discov 2011; 6: 393-404