Computational studies on the histone deacetylases and the design of selective histone deacetylase inhibitors

Current Topics in Medicinal Chemistry

Volumn 9, Issue 3, 2009, Pages 241-256

  Wang, Difei ^a  

^a NATIONAL CANCER INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

APHA 1; APHA 8; CG 1521; HISTONE DEACETYLASE; HISTONE DEACETYLASE 1; HISTONE DEACETYLASE 10; HISTONE DEACETYLASE 2; HISTONE DEACETYLASE 3; HISTONE DEACETYLASE 4; HISTONE DEACETYLASE 5; HISTONE DEACETYLASE 6; HISTONE DEACETYLASE 7; HISTONE DEACETYLASE 8; HISTONE DEACETYLASE 9; HISTONE DEACETYLASE INHIBITOR; N (2 AMINOPHENYL) 4 (3 PYRIDINYLMETHOXYCARBONYLAMINOMETHYL)BENZAMIDE; SIRTUIN 1; SIRTUIN 2; SIRTUIN 3; SIRTUIN 4; SIRTUIN 5; SIRTUIN 6; SIRTUIN 7; SK 658; SK 683; SK 691; SK 692; TRICHOSTATIN A; UNCLASSIFIED DRUG; UNINDEXED DRUG; VORINOSTAT;

APOPTOSIS; CANCER CELL CULTURE; CARCINOGENESIS; CELL CYCLE ARREST; CENTRAL NERVOUS SYSTEM DISEASE; CLINICAL TRIAL; DRUG DESIGN; DRUG EFFICACY; DRUG POTENCY; DRUG SELECTIVITY; DRUG TARGETING; ENZYME ACTIVE SITE; ENZYME ACTIVITY; ENZYME ANALYSIS; ENZYME INHIBITION; ENZYME STRUCTURE; HUMAN; HYDROPHOBICITY; MALARIA; MALIGNANT NEOPLASTIC DISEASE; MOLECULAR DYNAMICS; MOLECULAR MECHANICS; MOLECULAR MODEL; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PHARMACOPHORE; QUANTITATIVE STRUCTURE ACTIVITY RELATION; QUANTUM MECHANICS; REVIEW; SEQUENCE HOMOLOGY; SKIN LYMPHOMA; T CELL LYMPHOMA; X RAY CRYSTALLOGRAPHY;

COMPUTATIONAL BIOLOGY; DRUG DESIGN; ENZYME INHIBITORS; HISTONE DEACETYLASES; HUMANS; LIGANDS; MODELS, MOLECULAR; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 65449189558     PISSN: 15680266     EISSN: None     Source Type: Journal    
DOI: 10.2174/156802609788085287     Document Type: Review

References (92)

1. (a) Brownell, J. E.; Zhou, J.; Ranalli, T.; Kobayashi, R.; Edmondson, D. G.; Roth, S. Y.; Allis, C. D. Tetrahymena histone acetyltransferase A: a homolog to yeast Gcn5p linking histone acetylation to gene activation. Cell 1996, 84, 843-851.
2. (b) Bannister, A. J.; Kouzarides, T. The CBP co-activator is a histone acetyltransferase. Nature 1996, 384, 641-643.
3. (c) Ogryzko, V. V.; Schiltz, R. L.; Russanova, V.; Howard, B. H.; Nakatani, Y. The transcriptional coactivators p300 and CBP are histone acetyltransferases. Cell 1996, 87, 953-959.
4. (d) Taunton, J.; Hassig, C. A.; Schreiber, S. L. A mammalian histone deacetylase related to the yeast transcriptional regulator Rpd3p. Science 1996, 272, 408-411.
5. (e) Yang, W. M.; Inouye, C.; Zeng, Y.; Bearss, D.; Seto, E. Transcriptional repression by YY1 is mediated by interaction with a mammalian homolog of the yeast global regulator Rpd3. Proc. Natl. Acad. Sci. USA 1996, 93, 1285-12850.
6. (f) Rundlett, S. E.; Carmen, A. A.; Kobayashi, R.; Bavykin, S.; Turner, B. M.; Grunstein, M. HDA1 and RPD3 are members of distinct yeast histone deacetylase complexes that regulate silencing and transcription. Proc. Natl. Acad. Sci. USA 1996, 93, 14503-14508.
7. Wu, J.; Grunstein, M. 25 years after the nucleosome model: chromatin modifications. Trends Biochem. Sci. 2000, 25, 619-623.
8. Selected articles for HDAC related cancer diseases. (a) Bulter, L.M.; Agus, D. B.; Scher, H. I.; Higgins, B.; Rose, A.; Cordon-Cardo, C.; Thaler, H. T.; Rifkind, R. A.; Marks, P. A.; Richon, V. M. Suberoylanilide hydroxamic acid, an inhibitor of histone deacetylase, suppresses the growth of prostate cancer cells in vitro and in vivo. Cancer Res. 2000, 60, 5166-5170.
9. (b) Halkidou, K.; Gaughan, L.; Cook, S.; Leung, H. Y.; Neal, D. E.; Robson, C. N. Upregulation and nuclear recruitment of HDAC1 in hormone refractory prostate cancer. Prostate 2004, 59, 177-189.
10. (c) Wilson, A. J.; Byun, D. S.; Popova, N.; Murray, L. B.; L'Italien, K.; Sowa, Y.; Arango, D.; Velcich, A.; Augenlicht, L. H.; Mariadason, J. M. 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, 13548-13558.
11. (d) Zhang, Z.; Yamashita, H.; Toyama, T.; Sugiura, H.; Ando, Y.; Mita, K.; Hamaguchi, M.; Hara, Y.; Kobayashi, S.; Iwase, H. Breast Cancer Res. Treat. 2005, 94, 11-16.
12. (e) Zhang, Z.; Yamashita, H.; Toyama, T.; Sugiura, H.; Omoto, Y.; Ando, Y.; Mita, K.; Hamaguchi, M.; Hayashi, S.; Iwase, H. HDAC6 expression is correlated with better survival in breast cancer. Clin. Cancer Res. 2004, 10, 6962-6968.
13. (f) Zhu, P.; Martin, E.; Mengwasser, J.; Schlag, P.; Janssen, K. P.; Gottlicher, M. Induction of HDAC2 expression upon loss of APC in colorectal tumorigenesis. Cancer Cell 2004, 5, 455-463.
14. Bolden, J. E.; Peart, M. J.; and Johnstone, R. W. Anticancer activities of histone deacetylase inhibitors. Nat. Rev. Drug Discov. 2006, 5, 769-784.
15. Rasheed, W.; Bishton, M.; Johnstone, R. W.; Prince, H. M. Histone deacetylase inhibitors in lymphoma and solid malignancies. Expert Rev. Anticancer Ther. 2008, 8, 413-432.
16. Rasheed, W.; Johnstone, R. W.; Prince, H. M. Histone deacetylase inhibitors in cancer therapy. Expert Opin. Investig. Drugs 2007, 16, 659-678.
17. Kazantsev, A. G.; and Thompson, L. M. Nat. Rev. Drug Discov. 2008, 7, 854-868.
18. Meinke, P. T.; Colletti, S. L.; Doss, G.; Myers, R. W.; Gurnett, A. M.; Dulski, P. M.; Darkin-Rattray, S. J.; Allocco, J. J.; Galuska, S.; Schmatz, D. M.; Wyvratt, M. J.; Fisher, M. H. Synthesis of apicidin-derived quinolone derivatives: parasite-selective histone deacetylase inhibitors and antiproliferative agents. J. Med. Chem. 2000, 43, 4919-4922.
19. (a) De Ruijter, A. J.; Van Gennip, A. H.; Caron, H. N.; Kemp, S.; Van Kuilenburg, A. B. Histone deacetylases (HDACs): characterization of the classical HDAC family. Biochem. J. 2003, 370, 737-749.
20. (b) Gregoretti, I.; Lee, Y.-M.; Goodson, H. V. Molecular Evolution of the histone deacetylase family: functional implications of phylogenetic analysis. J. Mol. Biol. 2004, 338, 17-31.
21. Ahringer, J. NuRD and Sin3 histone deacetylase complexes in development. Trends Genet. 2000, 16, 351-356.
22. Wen, Y. D.; Perissi, V.; Staszewski, L. M.; Yang, W.; Krones, A.; Glass, C. K.; Rosenfeld, M. G.; Seto, E. The histone deacetylase-3 complex contains nuclear receptor corepressors. Proc. Natl. Acad. Sci. USA 2000, 97, 7202-7207.
23. (a) Martin, M.; Kettmann, R. and Dequiedt, F. Class IIa histone deacetylases: regulating the regulators. Oncogene 2007, 26, 5450-5467.
24. (b) Majdzadeh, N.; Morrison, B. E. and D'Mello, S. R. Class IIa HDACs in the regulation of neurodegeneration. Front. Biosci. 2008, 13, 1072-1082.
25. (a) Hubbert, C.; Guardiola, A.; Shao, R.; Kawaguchi, Y.; Ito, A.; Nixon, A.; Yoshida, M.; Wang, X. F.; Yao, T. P. HDAC6 is a microtubule-associated deacetylase. Nature 2002, 417, 455-458.
26. (b) Matsuyama A, Shimazu T, Sumida Y, Saito A, Yoshimatsu Y, Seigneurin-Berny D, Osada H, Komatsu Y, Nishino N, Khochbin S, Horinouchi S, Yoshida M. In vivo destabilization of dynamic microtubules by HDAC6-mediated deacetylation. EMBO J. 2002, 21, 6820-6831.
27. Gray, S. G.; Ekstrom, T. J. The human histone deacetylase family. Exp. Cell Res. 2001, 262, 75-83.
28. (a) Michan, S.; and Sinclair, D. Sirtuins in mammals: insights into their biological function. Biochem. J. 2007, 404, 1-13.
29. (b) Asher, G.; Gatfield, D.; Stratman, M.; Reinke, H.; Dibner, C.; Kreppel, F.; Mostoslavsky, R. Alt, F. W.; and Schibler, U. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell 2008, 134, 317-328.
30. +-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell 2008, 134, 329-340.
31. Carew, J. S.; Giles, F. J.; Nawrocki, S. T.; Histone deacetylase inhibitors: mechanisms of cell death and promise in combination cancer therapy. Cancer Lett. 2008, 269, 7-17.
32. Khan, O.; La Thangue, N. B. Drug insight: histone deacetylase inhibitor-based therapies for cutaneous T-cell lymphomas. Nat. Clin. Pract. Oncol. 2008, Oct 7.
33. Butler, K. V. and Kozikowski, A. P. Chemicla origins of isoform selectivity in histone deacetylase inhibitors. Curr. Pharm. Des. 2008, 14, 505-528
34. 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.
35. (a) 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.
36. (b) Vannini, A.; Volpari, C.; Filocamo, G.; Caroli Casavola, E.; Brunetti, M.; Renzoni, D.; Chakravarty, P.; Paolini, C.; De Francesco, R.; Gallinari, P.; Steinckuhler, C.; Di Marco, S. Crystal structure of a eukaryotic Zn-Dependent histone deacetylase, human HDAC8, complexed with a hydroxamic acid inhibitor. Proc. Nat. Acad. Sci. USA 2004, 101, 15064-15069.
37. Wang, D. -F.; Wiest, O.; Helquist, P.; Lan-Hargest, H. Y.; Wiech, N. L. On the function of the 14 Å long internal cavity of histone deacetylase-like protein: implications for the design of histone deacetylase inhibitors. J. Med. Chem. 2004, 47, 3409-3417.
38. Vannini, A.; Volpari, C.; Gallinari, P.; Jones, P.; Mattu, M.; Carfi, A.; De Francesco, R.; Steinkuhler, C.; and Di Marco, S. Substrate binding to histone deacetylases as shown by the crystal structure of the HDAC8-substrate complex. EMBO Rep. 2007, 8, 879-884.
39. 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.; and 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.
40. Bottomley, M. J.; Lo Surdo, P.; Di Giovine, P.; Cirillo, A.; Scarpelli, R.; Federica Ferrigno, F.; Jones, P.; Neddermann, P.; De Francesco, R.; Steinkuhler, C.; Gallinari, P. and Carfi, 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.
41. 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.
42. Finnin, M.S.; Donigian, J. R.; Pavletich, N. P. Structure of the histone deacetylase SIRT2. Nat. Struct. Biol. 2001, 8, 621-625.
43. +-dependent deacetylase SIRT5 by suramin. Structure 2007, 15, 377-389.
44. Zhao, K.; Chai, X.; Marmorstein, R. Structure of the yeast Hst2 protein deacetylase in ternary complex with 2′-O-acetyl ADP ribose and histone peptide. Structure 2003, 11, 1403-1411.
45. Avalos, J. L; Bever, K. M.; Wolberger, C. Structural basis for the mechanism and regulation of Sir2 enzymes. Mol. Cell. 2005, 17, 855-868.
46. Avalos, J. L; Boeke, J. D.; Wolberger, C. Mechanism of sirtuin inhibition by nicotinamide: altering the NAD(+) cosubstrate specificity of a Sir2 enzyme. Mol. Cell. 2004, 13, 639-648.
47. Chang, J. H.; Kim, H. C.; Hwang, K. Y.; Lee, J. W.; Jackson, S. P.; Bell, S. D.; Cho,Y. Structural basis for the NAD-dependent deacetylase mechanism of Sir2. J. Biol. Chem. 2002, 277, 34489-34498.
48. Zhao, K.; Chai, X.; Marmorstein, R. Structure and substrate binding properties of cobB, a Sir2 homolog protein deacetylase from Escherichia coli. J. Mol. Biol. 2004, 337, 731-741.
49. Park, H.; Lee, S. J. Homology modeling, force field design, and free energy simulation studies to optimize the activities of histone deacetylase inhibitors. J. Comput. Aided Mol. Des. 2004, 18, 375-388.
50. Massa, S.; Mai, A.; Sbardella, G.; Esposito, M.; Ragno, R.; Loidl, P.; Brosch, G. 3-(4-aroyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamides, a new class of synthetic histone deacetylase inhibitors. J. Med. Chem. 2001, 44, 2069-2072.
51. (a) Mai, A.; Massa, S.; Ragno, R.; Cerbara, I.; Jesacher, F.; Loidl, P.; Brosch, G. 3-(4-Aroyl-1-methyl-1H-2-pyrrolyl)-N-hydroxy-2-alkylamides as a new class of synthetic histone deacetylase inhibitors. 1. Design, synthesis, biological evaluation, and binding mode studies performed through three different docking procedures. J. Med. Chem. 2003, 46, 512-524.
52. (b) Mai, A.; Massa, S.; Cerbara, I.; Valente, S.; Ragno, R.; Bottoni, P.; Scatena, R.; Loidl, P.; Brosch, G. 3-(4-Aroyl-1-methyl-1H-2-pyrrolyl)-Nhydroxy-2-propenamides as a new class of synthetic histone deacetylase inhibitors. 2. Effect of pyrrole-C2 and/or -C4 substitutions on biological activity. J. Med. Chem. 2004, 47, 1098-1109.
53. (c) Ragno, R.; Mai, A.; Massa, S.; Cerbara, I.; Valente, S.; Bottoni, P.; Scatena, R.; Jesacher, F.; Loidl, P.; Brosch, G. 3-(4- Aroyl-1-methyl-1H-pyrrol-2-yl)-N-hydroxy-2-propenamides as a new class of synthetic histone deacetylase inhibitors. 3. Discovery of novel lead compounds through structure-based drug design and docking studies. J. Med. Chem. 2004, 47, 1351-1359.
54. Vanommeslaeghe, K.; Loverix, S.; Geerlings, P. and Tourwe, D. DFT-based ranking of zinc-binding groups in histone deacetylase inhibitors. Bioorg. Med. Chem. 2005, 13, 6070-6082.
55. Wang, D. -F.; Helquist, P. and Wiest, O. Zinc binding in HDAC inhibitors: A DFT study. J. Org. Chem. 2007, 72, 5446-5449.
56. Wang, D. -F.; Helquist, P.; Wiech, N. L.; 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.
57. (a) Moradei, O. M.; Mallais, T. C.; Frechette, S.; Paquin, I.; Tessier, P. E.; Leit, S. M.; Fournel, M.; Bonfils, C.; Trachy-Bourget, M. C.; Liu, J.; Yan, T. P.; Lu, A. H.; Rahil, J.; Wang, J.; Lefebvre, S.; Li, Z.; Vaisburg, A. F.; Besterman, J. M. Novel aminophenyl benzamide-type histone deacetylase inhibitors with enhanced potency and selectivity. J. Med. Chem. 2007, 50, 5543-5546.
58. (b) Methot, J. L.; Chakravarty P. K.; Chenard M.; Close, J.; Cruz, J. C.; Dahlberg, W. K.; Fleming, J.; Hamblett, C. L.; Hamill, J. E.; Harrington, P.; Harsch, A.; Heidebrecht, R.; Hughes, B.; Jung, J.; Kenific, C. M.; Kral, A. M.; Meinke, P. T.; Middleton, R. E.; Ozerova, N.; Sloman, D. L.; Stanton, M. G.; Szewczak, A. A.; Tyagarajan, S.; Witter, D. J.; Secrist, J. P. and Miller, T. A. Exploration of the internal cavity of histone deacetylase (HDAC) with selective HDAC1/HDAC2 inhibitors (SHI-1:2). Bioorg. Med. Chem. Lett. 2008, 18, 973-978.
59. Kim, H. M.; Hong, S. H.; Kim, M. S.; Lee, C. W.; Kang, J. S.; Lee, K.; Park, S. Y. Han, J. W.; Lee, H. Y.; Choi, Y.; Kwon, H. J.; Han, G. Modification of cap group in δ-lactam-based histone deacetylase (HDAC) inhibitors. Bioorg. Med. Chem. Lett. 2007, 17, 6234-6238.
60. Hamblett, C. L.; Methot, J. L.; Mampreian, D. M.; Sloman, D. L.; Stanton, M. G.; Kral, A. M.; Fleming, J. C.; Cruz, J. C.; Chenard, M.; Ozerova, N.; Hitz, A. M.; Wang, H.; Deshmukh, S. V.; Nazef, N.; Harsch, A.; Hughes, B.; Dahlberg, W. K.; Szewczak, A. A.; Middleton, R. E.; Mosley, R. T.; Secrist, J. P.; Miller, T. A. The discovery of 6-amino nicotinamides as potent and selective histone deacetylase inhibitors. Bioorg. Med. Chem. Lett. 2007, 17, 5300-5309.
61. Nakao, Y.; Yoshida, S.; Matsunaga, S.; Shindoh, N.; Terada, Y.; Nagai, K.; Yamashita, J. K.; Ganesan, A.; van Soest, R. W. M.; Fusetani, N. Azumamides A-E: histone deacetylase inhibitory cyclic tetrapeptides from the marine sponge Mycale izuensis. Angew. Chem. Int. Ed. 2006, 45, 7553-7557.
62. b) Izzo, I.; Maulucci, N.; Bifulco, G.; De Riccardis, F. Total synthesis of azumamides A and E. Angew. Chem. Int. Ed. 2006, 45, 7557-7560.
63. Maulucci, N.; Chini, M. G.; Micco, S. D.; Izzo, I.; Cafaro, E.; Russo, A.; Gallinari, P.; Paolini, C.; Nardi, M. C.; Casapullo, A.; Riccio, R.; Bifulco, G.; Riccardis, F. D. Molecular insights into azumamide E histone deacetylases inhibitory activity. J. Am. Chem. Soc. 2007, 129, 3007-3012.
64. Weerasinghe, S. V.; Estiu, G.; Wiest, O.; Pflum, M. K. Residues in the 11 Å channel of histone deacetylase 1 promote catalytic activity: implications for designing isoform-selective histone deacetylase inhibitors. J. Med. Chem. 2008, 51, 5542-5551.
65. Itoh, Y.; Suzuki, T.; Miyata, N. Isoform-selective histone deacetylase inhibitors. Curr. Pharm. Des. 2008, 14, 529-544.
66. Butler, K. V.; Kozikowski, A. P. Chemical origins of isoform selectivity in histone deacetylase inhibitors. Curr. Pharm. Des. 2008, 14, 505-528.
67. Haggarty, S. J.; Koeller, K. M.; Wong, J. C.; Grozinger, C. M.; Schreiber, S. L. Domain-selective small-molecule inhibitor of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation. Proc. Natl. Acad. Sci. USA 2003, 100, 4389-4394.
68. Suzuki, T.; Kouketsu, A.; Itoh, Y.; Hisakawa, S.; Maeda, S.; Yoshida, M.; Nakagawa, H.; Miyata, N. Highly potent and selective histone deacetylase 6 inhibitors designed based on a small-molecular substrate. J. Med. Chem. 2006, 49, 4809-4812.
69. 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.
70. Schafer, S.; Saunders, L.; Eliseeva, E.; Velena, A.; Jung, M.; Schwienhorst, A.; Strasser, A.; Dickmanns, A.; Ficner, R.; Schlimme, S.; Sippl, W.; Verdin, E.; Jung, M. Phenylalanine-containing hydroxamic acids as selective inhibitors of class IIb histone deacetylases (HDACs). Bioorg. Med. Chem. 2008, 16, 2011-2033.
71. Zhang, Y.; Gilquin, B.; Khochbin, S.; Matthias, P. Two catalytic domains are required for protein deacetylation. J. Biol. Chem. 2006, 281, 2401-2404.
72. Zou, H.; Wu, Y.; Navre, M.; Sang, B. C. Characterization of the two catalytic domains in histone deacetylase 6. Biochem. Biophys. Res. Commun. 2006, 341, 45-50.
73. Kozikowski, A. P.; Tapadar, S.; Luchini, D. N.; Kim, K. H.; and Billadeau, D. D. Use of the nitrile oxide cycloaddition (NOC) reaction for molecular probe generation: a new class of enzyme selective histone deacetylase inhibitors (HDACIs) showing picomolar activity at HDAC6. J. Med. Chem. 2008, 51, 4370-4373.
74. Estiu, G.; Greenberg, E.; Harrison, C. B.; Kwiatkowski, N. P.; Mazitschek, R.; Bradner, J.E. and Wiest, O. Structural origin of selectivity in class II-selective histone deacetylase inhibitors. J. Med. Chem. 2008, 51, 2898-2906.
75. Blander, G.; Guarente, L. The Sir2 family of protein deacetylases. Annu. Rev. Biochem. 2004, 73, 417-435.
76. Porcu, M.; Chiarugi, A. The emerging therapeutic potential of sirtuin-interacting drugs: from cell death to lifespan extension. Trends Pharmacol. Sci. 2005, 26, 94-103.
77. + dependent histone deacetylases (sirtuins). Curr. Pharm. Des. 2008, 14, 562-573.
78. Huhtiniemi, T.; Wittekindt, C.; Laitinen, T.; Leppanen, J.; Salminen, A.; Poso, A.; Lahtela-Kakkonen, M. Comparative and pharmacophore model for deacetylase SIRT1. J. Comput. Aided Mol. Des. 2006, 20, 589-599.
79. Neugebauer, R. C.; Uchiechowska, U.; Meier, R.; Hruby, H.; Valkov, V.; Verdin, E.; Sippl, W.; Jung, M. Structure-activity studies on splitomicin derivatives as sirtuin inhibitors and computational prediction of binding mode. J. Med. Chem. 2008, 51, 1203-1213.
80. Heltweg, B.; Gatbonton, T.; Schuler, A. D.; Posakony, J.; Li, H. Z.; Goehle, S.; Kollipara, R.; Depinho, R. A.; Gu, Y.; Simon, J. A.; Bedalov, A. Antitumor activity of a small-molecule inhibitor of human silent information regulator 2 enzymes. Cancer Res. 2006; 66, 4368-4377.
81. Qikprop 1.6, Schrodinger Inc. 2001. to calculate the properties. For publications, see Duffy, E. M.; Jorgensen, W. L. Prediction of properties from simulations: free energies of solvation in hexadecane, octanol, and water. J. Am. Chem. Soc. 2000, 122, 2878-2888.
82. (b) Jorgensen, W. L.; Duffy, E. M. Prediction of drug solubility from Monte Carlo simulations. Bioorg. Med. Chem. Lett. 2000, 10, 1155-1158.
83. Wang, D. -F.; Wiest, O.; Helquist, P.; Lan-Hargest, H. Y. and Wiech, N. L. QSAR studies of PC-3 cell line inhibition activity of TSA and SAHA-like hydroxamic acids. Bioorg. Med. Chem. Lett. 2004, 14, 707-711.
84. Xie, A.; Liao, C.; Li, Z.; Ning, Z.; Hu, W.; Lu, X.; Shi, L.; Zhou, J. Quantitative structure-activity relationship study of histone deacetylase inhibitors. Curr. Med. Chem. Anticancer Agents 2004, 4, 273-299.
85. Kozikowski, A.P.; Chen, Y.; Gaysin, A.M.; Savoy, D.N.; Billadeau, D.D.; Kim, K.H. Chemistry, biology, and QSAR studies of substituted biaryl hydroxamates and mercaptoacetamides as HDAC inhibitors-nanomolar-potency inhibitors of pancreatic cancer cell growth. ChemMedChem 2008, 3, 487-501.
86. Chen, H. -F.; Kang, J. -H.; Li, Q.; Zeng, B. -S.; Yao, X. -J.; Fan, B. -T.; Yuan, S.-G.; Panay, A.; Doucet, J. P. 3D-QSAR study on apicidin inhibit histone deacetylase. Chin. J. Chem. 2003, 21, 1596-1607.
87. Guo, Y.; Xiao, J.; Guo, Z.; Chu, F.; Cheng, Y. and Wu, S. Exploration of a binding mode of indole amide analogues as potent histone deacetylase inhibitors and 3D-QSAR analyses. Bioorg. Med. Chem. 2005, 13, 5424-5434.
88. Juvale, D. C.; Kulkarni, V. V.; Deokar, H. S.; Wagh, N. K.; Padhye, S. B.; Kulkarni, V. M. 3D-QSAR of histone deacetylase inhibitors: hydroxamate analogues. Org. Biomol. Chem. 2006, 15, 2858-2868.
89. Chen, Y. D.; Jiang, Y. J.; Zhou, J. W.; Yu, Q. S.; You, Q. D. Identification of ligand features essential for HDACs inhibitors by pharmacophore modeling. J. Mol. Graph. Model. 2008, 26, 1160-1168.
90. Ragno, R.; Simeoni, S.; Rotili, D.; Caroli, A.; Botta, G.; Brosch, G.; Massa, S.; Mai, A. Class II-selective histone deacetylase inhibitors. Part 2: Alignment-independent GRIND 3-D QSAR, homology and docking studies. Eur. J. Med. Chem. 2008, 43, 621-632.
91. Avalos, J. L.; Celic, I.; Muhammad, S.; Cosgrove, M. S.; Boeke, J. D.; Wolberger, C. Structure of a Sir2 enzyme bound to an acetylated p53 peptide. Mol. Cell 2002, 10, 523-535.
92. Min, J.; Landry, J.; Sternglanz, R.; Xu, R. M. Crystal structure of a SIR2 homolog-NAD complex. Cell 2001, 105, 269-276.