Synthesis and biological characterization of the histone deacetylase inhibitor largazole and C7- modified analogues

Journal of Medicinal Chemistry

Volumn 53, Issue 12, 2010, Pages 4654-4667

  Souto, José A ^a   Vaz, Esther ^a   Lepore, Ilaria ^b   Pöppler, Ann Christin ^a   Franci, Gianluigi ^b,c   Álvarez, Rosana ^a   Altucci, Lucia ^b,c   De Lera, Ángel R ^a  

^a UNIVERSITY OF VIGO   (Spain)

^b SECOND UNIVERSITY OF NAPLES   (Italy)

^c INSTITUTE OF GENETICS AND BIOPHYSICS ADRIANO BUZZATI TRAVERSO   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA TUBULIN; CYCLIN DEPENDENT KINASE INHIBITOR 1; HISTONE DEACETYLASE 1; HISTONE DEACETYLASE INHIBITOR; HISTONE H3; LARGAZOLE; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; CELL DIFFERENTIATION; DRUG SELECTIVITY; DRUG SYNTHESIS; ENZYME INHIBITION; GRANULOCYTE; HUMAN; HUMAN CELL; IN VITRO STUDY; LEUKEMIA CELL; STRUCTURE ACTIVITY RELATION; UPREGULATION;

ACETYLATION; ANTIGENS, CD11C; ANTINEOPLASTIC AGENTS; APOPTOSIS; CELL DIFFERENTIATION; CELL LINE, TUMOR; CYCLIN-DEPENDENT KINASE INHIBITOR P21; DEPSIPEPTIDES; DRUG SCREENING ASSAYS, ANTITUMOR; GRANULOCYTES; HISTONE DEACETYLASE 1; HISTONE DEACETYLASE INHIBITORS; HISTONE DEACETYLASES; HUMANS; RECOMBINANT PROTEINS; REPRESSOR PROTEINS; STEREOISOMERISM; STRUCTURE-ACTIVITY RELATIONSHIP; THIAZOLES; TUBULIN;

EID: 77953740289     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm100244y     Document Type: Article

References (70)

1. Egger, G.; Liang, G.; Jones, P. A. Epigenetics in human disease and prospects for epigenetic therapy Nature 2004, 429, 457-463
2. Esteller, M. Epigenetics in Cancer N. Engl. J. Med. 2008, 358, 1148-1159
3. Biel, M.; Wascholowski, V.; Giannis, A. Epigenetics-an epicenter of gene regulation: histones and histone-modifying enzymes Angew. Chem., Int. Ed. 2005, 44, 3186-3216
4. Allis, C. D.; Jenuwein, T.; Reinberg, D.; Caparros, M.-L. Epigenetics; Cold Spring Harbor Laboratory Press: Cold Spring Harbor, NY, 2007.
5. Sippl, W.; Jung, M., Eds. Epigenetic Targets in Drug Discovery. In Methods and Principles of Medicinal Chemistry, Vol. 42; Mannhold, R.; Kubinyi, H.; Folkers, G., Series Eds.; Wiley-VCH: Weinheim, 2009.
6. Mellert, H. S.; McMahon, S. B. Biochemical pathways that regulate acetyltransferase and deacetylase activity in mammalian cells Trends Biochem. Sci. 2009, 34, 571-578
7. Shahbazian, M. D.; Grundstein, M. Functions of site-specific histone acetylation and deacetylation Annu. Rev. Biochem. 2007, 76, 75-100
8. Hodawadekar, S. C.; Marmorstein, R. Chemistry of acetyl transfer by histone modifying enzymes: structure, mechanism and implications for effector design Oncogene 2007, 26, 5528-5540
9. Minucci, S.; Pelicci, P. G. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer Nature Rev. Cancer 2006, 6, 38-51
10. Bolden, J. E.; Peart, M. J.; Johnstone, R. W. Anticancer activities of histone deacetylase inhibitors Nature Rev. Drug Discovery 2006, 5, 769-784
11. Smith, K. T.; Workman, J. L. Histone deacetylase inhibitors: Anticancer compounds Int. J. Biochem. Cell Biol. 2009, 41, 21-25
12. Mai, A.; Altucci, L. Epi-drugs to fight cancer: From chemistry to cancer treatment, the road ahead Int. J. Biochem. Cell Biol. 2009, 41, 199-213
13. Bieliauskas, A. V.; Pflum, M. K. H. Isoform-selective histone deacetylase inhibitors Chem. Soc. Rev. 2008, 37, 1402-1413
14. De Ruijter, A. J. M.; Van Gennip, A. H.; Caron, H. N.; Kemp, S.; Van Kuilenburg, A. B. P. Histone deacetylases (HDACs): characterization of the classical HDAC family Biochem. J. 2003, 370, 737-749
15. Grozinger, C. M.; Schreiber, S. L. Deacetylase enzymes: biological functions and the use of small-molecule inhibitors Chem. Biol. 2002, 9, 3-16
16. Corminboeuf, C.; Hu, P.; Tuckerman, M. E.; Zhang, Y. Unexpected deacetylation mechanism suggested by a density functional theory QM/MM study of histone-deacetylase-like protein J. Am. Chem. Soc. 2006, 128, 4530-4531
17. Paris, M.; Porcelloni, M.; Binaschi, M.; Fattori, D. Histone Deacetylase Inhibitors: From Bench to Clinic J. Med. Chem. 2008, 51, 1505-1529
18. Finnin, M. S.; Donigian, J. R.; Cohen, A.; Richon, V. M.; Rifkind, R. A.; Marks, P. A.; Breslow, R.; Pavletich, N. P. Structures of a histone deacetylase homologue bound to the TSA and SAHA inhibitors Nature 1999, 401, 188-193
19. Somoza, J. R.; Skene, R. J.; Katz, B. A.; Mol, C.; Ho, J. D.; Jennings, A. J.; Luong, C.; Arvai, A.; Buggy, J. J.; Chi, E.; Tang, J.; Sang, B. C.; Verner, E.; Wynands, R.; Leahy, E. M.; Dougan, D. R.; Snell, G.; Navre, M.; Knuth, M. W.; Swanson, R. V.; McRee, D. E.; Tari, L. W. Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases Structure 2004, 12, 1325-1334
20. Vannini, A.; Volpari, C.; Filocamo, G.; Casavola, E. C.; Brunetti, M.; Renzoni, D.; Chakravarty, P.; Paolini, C.; De Francesco, R.; Gallinari, P.; Steinkühler, C.; Di Marco, S. Crystal structure of a eukaryotic zinc-dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 15064-15069
21. Nielsen, T. K.; Hildmann, C.; Dickmanns, A.; Schwienhorst, A.; Ficner, R. Crystal structure of a bacterial class 2 histone deacetylase homologue J. Mol. Biol. 2005, 354, 107-120
22. Schuetz, A.; Min, J.; Allali-Hassani, A.; Schapira, M.; Shuen, M.; Loppnau, P.; Mazitschek, R.; Kwiatkowski, N. P.; Lewis, T. A.; Maglathin, R. L.; McLean, T. H.; Bochkarev, A.; Plotnikov, A. N.; Vedadi, M.; Arrowsmith, C. H. Human HDAC7 Harbors a Class IIa Histone Deacetylase-Specific Zinc Binding Motif and Cryptic Deacetylase Activity J. Biol. Chem. 2008, 283, 11355-11363
23. Bottomley, M. J.; Lo Surdo, P.; Di Giovine, P.; Cirillo, A.; Scarpelli, R.; Ferrigno, F.; Jones, P.; Neddermann, P.; De Francesco, R.; Steinkühler, C.; Gallinari, P.; Carfí, A. Structural and Functional Analysis of the Human HDAC4 Catalytic Domain Reveals a Regulatory Structural Zinc-Binding Domain J. Biol. Chem. 2008, 283, 26694-26704
24. Newkirk, T. L.; Bowers, A. A.; Williams, R. M. Discovery, biological activity, synthesis and potential therapeutic utility of naturally occurring histone deacetylase inhibitors Nat. Prod. Rep. 2009, 26, 1293-1320
25. Okuhara, M.; Goto, T.; Fujita, T.; Hori, Y.; Ueda, H. FR901375 substance and production thereof (Fujisawa Pharmaceutical Co, Ltd) Japanese Patent JP 03141296. Jpn. Kokai Tokkyo Koho 1991.
26. Ueda, H.; Nakajima, H.; Hori, Y.; Fujita, T.; Nishimura, M.; Goto, T.; Okuhara, M. 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, 301-310
27. Shigematsu, N.; Ueda, H.; Takase, S.; Tanaka, H.; Yamamoto, K.; Tada, T. FR901228, a novel antitumor bicyclic depsipeptide produced by Chromobacterium violaceum No. 968. II. Structure determination J. Antibiot. 1994, 47, 311-314 (Pubitemid 24106521)
28. Masuoka, Y.; Nagai, A.; Shin-ya, K.; Furihata, K.; Nagai, K.; Suzuki, K.-i.; Hayakawa, Y.; Seto, H. Spiruchostatins A and B, novel gene expression-enhancing substances produced by Pseudomonas sp Tetrahedron Lett. 2001, 42, 41-44
29. Taori, K.; Paul, V. J.; Luesch, H. Structure and Activity of Largazole, a Potent Antiproliferative Agent from the Floridian Marine Cyanobacterium Symploca sp J. Am. Chem. Soc. 2008, 130, 1806-1807
30. Bach, R. D.; Dmitrenko, O.; Thorpe, C. Mechanism of thiolate-disulfide interchange reactions in Biochemistry J. Org. Chem. 2008, 73, 12-21
31. Furumai, R.; Matsuyama, A.; Kobashi, N.; Lee, K. H.; Nishiyama, M.; Nakajima, H.; Tanaka, A.; Komatsu, Y.; Nishino, N.; Yoshida, M.; Horinouchi, S. FK228 (depsipeptide) as a natural prodrug that inhibits class I histone deacetylases Cancer Res. 2002, 62, 4916-4921
32. Xiao, J. J.; Byrd, J.; Marcucci, G.; Grever, M.; Can, K. K. Identification of thiols and glutathione conjugates of depsipeptide FK228 (FR901228), a novel histone protein deacetylase inhibitor, in the blood Rapid Commun. Mass Spectrom. 2003, 17, 757-766
33. Wang, D.; Helquist, P.; Wiest, O. Zinc Binding in HDAC Inhibitors: A DFT Study J. Org. Chem. 2008, 72, 5446-5449
34. 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, 8455-8459
35. Bowers, A.; West, N.; Taunton, J.; Schreiber, S. L.; Bradner, J. E.; Williams, R. M. Total Synthesis and Biological Mode of Action of Largazole: A Potent Class I Histone Deacetylase Inhibitor J. Am. Chem. Soc. 2008, 130, 11219-11222
36. Ying, Y.; Liu, Y.; Byeon, S. R.; Kim, H. S.; Luesch, H.; Hong, J. Synthesis and Activity of Largazole Analogues with Linker and Macrocycle Modification Org. Lett. 2008, 10, 4021-4024
37. Nasveschuk, C. G.; Ungermannova, D.; Liu, X.; Phillips, A. J. A Concise Total Synthesis of Largazole, Solution Structure, and Some Preliminary Structure-Activity Relationships Org. Lett. 2008, 10, 3595-3598
38. Seiser, T.; Kamena, F.; Cramer, N. Synthesis and Biological Activity of Largazole and Derivatives Angew. Chem., Int. Ed. 2008, 47, 6483-6485
39. Ghosh, A. K.; Kulkarni, S. Enantioselective Total Synthesis of (+)-Largazole, a Potent Inhibitor of Histone Deacetylase Org. Lett. 2008, 10, 3907-3909
40. Ren, Q.; Dai, L.; Zhang, H.; Tan, W.; Xu, Z.; Ye, T. Total Synthesis of Largazole Synlett 2008, 2379-2383
41. Bowers, A. A.; West, N.; Newkirk, T. L.; Troutman-Youngman, A. E.; Schreiber, S. L.; Wiest, O.; Bradner, J. E.; Williams, R. M. Synthesis and Histone Deacetylase Inhibitory Activity of Largazole Analogs: Alteration of the Zinc-Binding Domain and Macrocyclic Scaffold Org. Lett. 2009, 11, 1301-1304
42. Bowers, A. A.; Greshock, T. J.; West, N.; Estiu, G.; Schreiber, S. L.; Wiest, O.; Williams, R. M.; Bradner, J. E. Synthesis and Conformation-Activity Relationships of the Peptide Isosteres of FK228 and Largazole J. Am. Chem. Soc. 2009, 131, 2900-2905
43. Chen, F.; Gao, A.-H.; Li, J.; Nan, F.-J. Synthesis and Biological Evaluation of C7-Demethyl Largazole Analogues ChemMedChem 2009, 4, 1269-1272
44. Wang, B.; Forsyth, C. J. Total synthesis of largazole-Devolution of a novel synthetic strategy Synlett 2009, 2873-2880
45. Li, K. W.; Wu, J.; Xing, W.; Simon, J. A. Total synthesis of the antitumor depsipeptide FR-901,228 J. Am. Chem. Soc. 1996, 118, 7237-7238
46. Wen, S.; Packham, G.; Ganesan, A. Macrolactamization versus Macrolactonization: Total Synthesis of FK228, the Depsipeptide Histone Deacetylase Inhibitor J. Org. Chem. 2008, 73, 9353-9361
47. Connon, S. J.; Blechert, S. Recent Developments in Olefin Cross-Metathesis Angew. Chem., Int. Ed. 2003, 42, 1900-1923
48. Pattenden, G.; Thom, S. M.; Jones, M. F. Enantioselective Synthesis of 2-alkyl substituted cysteines Tetrahedron 1993, 49, 2131-2138
49. Tan, C.-H.; Holmes, A. B. The Synthesis of (+)-Allopumiliotoxin 323B′ Chem.-Eur. J. 2001, 7, 1845-1854
50. Videnov, G.; Kaiser, D.; Kempter, C.; Jung, G. Synthesis of Naturally Occurring, Conformationally Restricted Oxazole- and Thiazole-Containing Di- and Tripeptide Mimetics Angew. Chem., Int. Ed. 1996, 35, 1503-1506
51. Lange, U. E. W.; Schäfer, B.; Baucke, D.; Buschmann, E.; Mack, H. A new mild method for the synthesis of amidines Tetrahedron Lett. 1999, 40, 7067-7070
52. Lloyd-Williams, P.; Albericio, F.; Giralt, E. Chemical Approaches to the Synthesis of Peptides and Proteins; CRC: Boca Raton, FL, 1997.
53. Han, S.-Y.; Kim, Y.-A. Recent development of peptide coupling reagents in organic synthesis Tetrahedron 2004, 60, 2447-2467
54. Davies, J. S. The cyclization of peptides and depsipeptides J. Peptide Sci. 2003, 9, 471-501
55. Marks, P. A. Discovery and development of SAHA as an anticancer agent Oncogene 2007, 26, 1351-1356
56. Rosato, R. R.; Grant, S. Histone deacetylase inhibitors in cancer therapy Cancer Biol. Ther. 2003, 2, 30-37
57. Mai, A.; Massa, S.; Pezzi, R.; Simeoni, S.; Rotili, D.; Nebbioso, A.; Scognamiglio, A.; Altucci, L.; Loidl, P.; Brosch, G. Class II (IIa)-selective histone deacetylase inhibitors. 1. Synthesis and biological evaluation of novel (aryloxopropenyl)pyrrolyl hydroxyamides J. Med. Chem. 2005, 48, 3344-3353
58. Jiménez-Lara, A. M.; Clarke, N.; Altucci, L.; Gronemeyer, H. Retinoic-acid-induced apoptosis in leukemia cells Trends Mol. Med. 2004, 10, 508-515
59. Altucci, L.; Clarke, N.; Nebbioso, A.; Scognamiglio, A.; Gronemeyer, H. Acute myeloid leucemia: therapeutic impact of epigenetic drugs Int. J. Biochem. Cell Biol. 2005, 37, 1752-1762
60. Baylin, S. B.; Ohm, J. E. Epigenetic gene silencing in cancer-A mechanism for early oncogenic pathway addiction? Nature Rev. Cancer 2006, 6, 107-116
61. Yoo, C. B.; Jones, P. A. Epigenetic therapy of cancer: past, present and future Nature Rev. Drug Discovery 2006, 5, 37-50
62. Marmorstein, R. Protein modules that manipulate histone tails for chromatin regulation Nat. Rev. Mol. Cell. Biol. 2001, 2, 422-432
63. Cloos, P. A. C.; Christensen, J.; Agger, K.; Helin, K. Erasing the methyl mark: histone demethylases at the center of cellular differentiation and disease Genes Dev. 2008, 22, 1115-1140
64. Ellis, L.; Atadja, P. W.; Johnstone, R. W. Epigenetics in cancer: targeting chromatin modifications Mol. Cancer Ther. 2009, 8, 1409-1420
65. Spannhoff, A.; Hauser, A.-T.; Heinke, R.; Sippl, W.; Jung, M. The Emerging Therapeutic Potential of Histone Methyltransferase and Demethylase Inhibitors ChemMedChem 2009, 4, 1568-1582
66. Insinga, A.; Monestiroli, S.; Ronzoni, S.; Gelmetti, V.; Marchesi, F.; Viale, A.; Altucci, L.; Nervi, C.; Minucci, S.; Pelicci, P. G. Inhibitors of histone deacetylases induce tumor-selective apoptosis through activation of the death receptor pathway Nature Med. 2005, 11, 71-76
67. Nebbioso, A.; Clarke, N.; Voltz, E.; Germain, E.; Ambrosino, C.; Bontempo, P.; Alvarez, R.; Schiavone, E. M.; Ferrara, F.; Bresciani, F.; Weisz, A.; de Lera, A. R.; Gronemeyer, H.; Altucci, L. Tumor-selective action of HDAC inhibitors involves TRAIL induction in acute myeloid leukemia cells Nature Med. 2005, 11, 77-84
68. Lanotte, M.; Martin-Thouvenin, V.; Najman, S.; Balerini, P.; Valensi, F.; Berger, R. NB4, a maturation inducible cell line with t(15;17) marker isolated from a human acute promyelocytic leukemia (M3) Blood 1991, 77, 1080-1086
69. Suzuki, T.; Nagano, Y.; Kouketsu, A.; Matsuura, A.; Maruyama, S.; Kurotaki, M.; Nakagawa, H.; Miyata, N. Novel inhibitors of human histone deacetylases: design, synthesis, enzyme inhibition, and cancer cell growth inhibition of SAHA-based non-hydroxamates J. Med. Chem. 2005, 48, 1019-1032
70. Suzuki, T.; Hisakawa, S.; Itoh, Y.; Maruyama, S.; Kurotaki, M.; Nakagawa, H.; Miyata, N. Identification of a potent and stable antiproliferative agent by the prodrug formation of a thiolate histone deacetylase inhibitor Bioorg. Med. Chem. Lett. 2007, 17, 1558-1561