Design and optimization of novel hydroxamate-based histone deacetylase inhibitors of bis-substituted aromatic amides bearing potent activities against tumor growth and metastasis

Journal of Medicinal Chemistry

Volumn 57, Issue 22, 2014, Pages 9357-9369

  Yang, Feifei ^a   Zhang, Tao ^a   Wu, Haigang ^a   Yang, Yang ^a   Liu, Ning ^a   Chen, Ang ^a   Li, Qiang ^a   Li, Jingjie ^a   Qin, Liwen ^a   Jiang, Beier ^a   Wang, Xin ^a   Pang, Xiufeng ^a   Yi, Zhengfang ^a   Liu, Mingyao ^a   Chen, Yihua ^a  

^a EAST CHINA NORMAL UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; AROMATIC AMIDE; HISTONE DEACETYLASE INHIBITOR; HYDROXAMIC ACID DERIVATIVE; N 1 (2 METHOXYPHENYL) N 7 HYDROXY N 1 [(3 PYRIDINYL)METHYL]HEPTANEDIAMIDE; N 1 (2 METHOXYPHENYL) N 7 HYDROXY N 1 [(4 BROMO 2 THIOPHENEYL)METHYL]HEPTANEDIAMIDE; N 1 (2 METHOXYPHENYL) N 7 HYDROXY N 1 [(5 BROMO 2 FURANYL)METHY]HEPTANEDIAMIDE; N 1 (2 METHOXYPHENYL) N 7 HYDROXY N 1 [(5 BROMO 2 THIOPHENEYL)METHYL]HEPTANEDIAMIDE; N 1 (2 METHOXYPHENYL) N 7 HYDROXY N 1 [(5 CHLORO 2 THIOPHENEYL)METHYL]HEPTANEDIAMIDE; N 1 (2 METHOXYPHENYL) N 7 HYDROXY N 1 [(6 BROMO 2 PYRIDINYL)METHYL]HEPTANEDIAMIDE; N 1 (2 METHOXYPHENYL) N 7 HYDROXY N 1 [[5 (3 PYRIDINYL) 2 THIOPHENEYL]METHYL]HEPTANEDIAMIDE; N 1 (2 METHOXYPHENYL) N 7 HYDROXY N 1 [[5 (4 PYRIDINYL) 2 THIOPHENEYL]METHYL]HEPTANEDIAMIDE; N 1 (2 METHOXYPHENYL) N 7 HYDROXY N 1 [[5 (5 PYRIDINYL) 2 THIOPHENEYL]METHYL]HEPTANEDIAMIDE; N 1 (3 BROMOBENZYL) N 4 HYDROXY N 1 (2 METHOXYPHENYL)SUCCINAMIDE; N 1 (3 BROMOBENZYL) N 5 HYDROXY N 1 (2 METHOXYPHENYL)GLUTARAMIDE; N 1 (3 BROMOBENZYL) N 6 HYDROXY N 1 (2 METHOXYPHENYL)ADIPAMIDE; N 1 (3 BROMOBENZYL) N 7 HYDROXY N 1 (2 CHLOROPHENYL)HEPTANEDIAMIDE; N 1 (3 BROMOBENZYL) N 7 HYDROXY N 1 (2 METHOXYPHENYL)HEPTANEDIAMIDE; N 1 (3 BROMOBENZYL) N 7 HYDROXY N 1 (3 CHLOROPHENYL)HEPTANEDIAMIDE; N 1 (3 BROMOBENZYL) N 7 HYDROXY N 1 (3 METHOXYPHENYL)HEPTANEDIAMIDE; N 1 (3 BROMOBENZYL) N 7 HYDROXY N 1 (4 BROMOPHENYL)HEPTANEDIAMIDE; N 1 (3 BROMOBENZYL) N 7 HYDROXY N 1 (4 CHLOROPHENYL)HEPTANEDIAMIDE; N 1 (3 BROMOBENZYL) N 7 HYDROXY N 1 (4 FLUOROPHENYL)HEPTANEDIAMIDE; N 1 (3 BROMOBENZYL) N 7 HYDROXY N 1 (4 IODOPHENYL)HEPTANEDIAMIDE; N 1 (3 BROMOBENZYL) N 7 HYDROXY N 1 (4 METHOXYPHENYL)HEPTANEDIAMIDE; N 1 (3 BROMOBENZYL) N 7 HYDROXY N 1 PHENYLHEPTANEDIAMIDE; N 1 [(5 BROMO 2 THIOPHENYL)METHYL] N 7 HYDROXY N 1 (4 METHOXYPHENYL)HEPTANEDIAMIDE; N 1 [[5 (5 PYRIMIDINYL) 2 THIOPHENEYL]METHYL] N 7 HYDROXY N 1 (4 METHOXYPHENYL)HEPTANEDIAMIDE; N [[5 (3 PYRIDINYL) 2 THIOPHENEYL]METHYL] N (2 METHOXYPHENYL)PIMELIC ACID METHYL ESTER; UNCLASSIFIED DRUG; VORINOSTAT; AMIDE; HYDROXAMIC ACID;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; ANTIPROLIFERATIVE ACTIVITY; AREA UNDER THE CURVE; ARTICLE; BREAST CANCER CELL LINE; BREAST TUMOR; CANCER INHIBITION; CELL MIGRATION; CELL PROLIFERATION; CONTROLLED STUDY; DOSE RESPONSE; DRUG CLEARANCE; DRUG DESIGN; DRUG EFFICACY; DRUG HALF LIFE; DRUG IDENTIFICATION; DRUG POTENCY; DRUG SYNTHESIS; FEMALE; HUMAN; HUMAN CELL; IC50; IN VITRO STUDY; IN VIVO STUDY; LUNG METASTASIS; MAXIMUM PLASMA CONCENTRATION; MEAN RESIDENCE TIME; METASTASIS INHIBITION; MOUSE; NONHUMAN; REACTION OPTIMIZATION; STRUCTURE ACTIVITY RELATION; TIME TO MAXIMUM PLASMA CONCENTRATION; TREATMENT RESPONSE; TUMOR XENOGRAFT; ACETYLATION; ANIMAL; BREAST NEOPLASMS; CELL MOTION; CHEMISTRY; DRUG SCREENING; METASTASIS; NEOPLASMS; TUMOR CELL LINE; TUMOR INVASION;

ACETYLATION; AMIDES; ANIMALS; BREAST NEOPLASMS; CELL LINE, TUMOR; CELL MOVEMENT; CELL PROLIFERATION; DRUG DESIGN; FEMALE; HISTONE DEACETYLASE INHIBITORS; HUMANS; HYDROXAMIC ACIDS; INHIBITORY CONCENTRATION 50; MICE; NEOPLASM INVASIVENESS; NEOPLASM METASTASIS; NEOPLASMS; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84913554345     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm5012148     Document Type: Article

References (51)

1. Jenuwein, T.; Allis, C. D. Translating the histone code Science 2001, 293, 1074-1080
2. Kouzarides, T. Chromatin modifications and their function Cell 2007, 128, 693-705
3. Hassig, C. A.; Schreiber, S. L. Nuclear histone acetylases and deacetylases and transcriptional regulation: HATs off to HDACs Curr. Opin. Chem. Biol. 1997, 1, 300-308
4. Witt, O.; Deubzer, H. E.; Milde, T.; Oehme, I. HDAC family: What are the cancer relevant targets? Cancer Lett. 2009, 277, 8-21
5. 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
6. He, R.; Chen, Y.; Chen, Y.; Ougolkov, A. V.; Zhang, J. S.; Savoy, D. N.; Billadeau, D. D.; Kozikowski, A. P. Synthesis and biological evaluation of triazol-4-ylphenyl-bearing histone deacetylase inhibitors as anticancer agents J. Med. Chem. 2010, 53, 1347-1356
7. Mwakwari, S. C.; Guerrant, W.; Patil, V.; Khan, S. I.; Tekwani, B. L.; Gurard-Levin, Z. A.; Mrksich, M.; Oyelere, A. K. Non-peptide macrocyclic histone deacetylase inhibitors derived from tricyclic ketolide skeleton J. Med. Chem. 2010, 53, 6100-6111
8. Paris, M.; Porcelloni, M.; Binaschi, M.; Fattori, D. Histone deacetylase inhibitors: From bench to clinic J. Med. Chem. 2008, 51, 1505-1529
9. Bolden, J. E.; Peart, M. J.; Johnstone, R. W. Anticancer activities of histone deacetylase inhibitors Nat. Rev. Drug Discovery 2006, 5, 769-784
10. Marks, P.; Rifkind, R. A.; Richon, V. M.; Breslow, R.; Miller, T.; Kelly, W. K. Histone deacetylases and cancer: Causes and therapies Nat. Rev. Cancer 2001, 1, 194-202
11. Thaler, F.; Mercurio, C. Towards selective inhibition of histone deacetylase isoforms: What has been achieved, where we are and what will be next ChemMedChem. 2014, 9, 523-526
12. Bradner, J. E.; West, N.; Grachan, M. L.; Greenberg, E. F.; Haggarty, S. J.; Warnow, T.; Mazitschek, R. Chemical phylogenetics of histone deacetylases Nat. Chem. Biol. 2010, 6, 238-243
13. Zhang, L.; Han, Y.; Jiang, Q.; Wang, C.; Chen, X.; Li, X.; Xu, F.; Jiang, Y.; Wang, Q.; Xu, W. Trend of histone deacetylase inhibitors in cancer therapy: Isoform selectivity or multitargeted strategy Med. Res. Rev. 2014, 10.1002/med.21320
14. Glauben, R.; Sonnenberg, E.; Zeitz, M.; Siegmund, B. HDAC inhibitors in models of inflammation-related tumorigenesis Cancer Lett. 2009, 280, 154-159
15. 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
16. Marks, P. A. Discovery and development of SAHA as an anticancer agent Oncogene 2007, 26, 1351-1356
17. Minucci, S.; Pelicci, P. G. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer Nat. Rev. Cancer 2006, 6, 38-51
18. Iwata, S.; Saito, T.; Ito, Y.; Kamakura, M.; Gotoh, K.; Kawada, J.; Nishiyama, Y.; Kimura, H. Antitumor activities of valproic acid on Epstein-Barr virus-associated T and natural killer lymphoma cells Cancer Sci. 2012, 103, 375-381
19. Monneret, C. Histone deacetylase inhibitors Eur. J. Med. Chem. 2005, 40, 1-13
20. Yoo, C. B.; Jones, P. A. Epigenetic therapy of cancer: Past, present and future Nat. Rev. Drug Discovery 2006, 5, 37-50
21. Grant, S.; Easley, C.; Kirkpatrick, P. Vorinostat Nat. Rev. Drug Discovery 2007, 6, 21-22
22. 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
23. http://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm403960.htm.
24. Giannini, G.; Cabri, W.; Fattorusso, C.; Rodriquez, M. Histone deacetylase inhibitors in the treatment of cancer: Overview and perspectives Future Med. Chem. 2012, 4, 1439-1460
25. Gryder, B. E.; Sodji, Q. H.; Oyelere, A. K. Targeted cancer therapy: Giving histone deacetylase inhibitors all they need to succeed Future Med. Chem. 2012, 4, 505-524
26. Christofori, G. New signals from the invasive front Nature 2006, 441, 444-450
27. Mehlen, P.; Puisieux, A. Metastasis: A question of life or death Nat. Rev. Cancer 2006, 6, 449-458
28. Zheng, C.; Fang, Y.; Tong, W.; Li, G.; Wu, H.; Zhou, W.; Lin, Q.; Yang, F.; Yang, Z.; Wang, P.; Peng, Y.; Pang, X.; Yi, Z.; Luo, J.; Liu, M.; Chen, Y. Synthesis and biological evaluation of novel tetrahydro-beta-carboline derivatives as antitumor growth and metastasis agents through inhibiting the transforming growth factor-beta signaling pathway J. Med. Chem. 2014, 57, 600-612
29. Li, X.; Inks, E. S.; Li, X.; Hou, J.; Chou, C. J.; Zhang, J.; Jiang, Y.; Zhang, Y.; Xu, W. Discovery of the first N -hydroxycinnamamide-based histone deacetylase 1/3 dual inhibitors with potent oral antitumor activity J. Med. Chem. 2014, 57, 3324-3341
30. Miller, T. A.; Witter, D. J.; Belvedere, S. Histone deacetylase inhibitors J. Med. Chem. 2003, 46, 5097-5116
31. Morine, Y.; Shimada, M.; Iwahashi, S.; Utsunomiya, T.; Imura, S.; Ikemoto, T.; Mori, H.; Hanaoka, J.; Miyake, H. Role of histone deacetylase expression in intrahepatic cholangiocarcinoma Surgery 2012, 151, 412-419
32. Shen, J.; Woodward, R.; Kedenburg, J. P.; Liu, X.; Chen, M.; Fang, L.; Sun, D.; Wang, P. G. Histone deacetylase inhibitors through click chemistry J. Med. Chem. 2008, 51, 7417-7427
33. Nolen, B. J.; Tomasevic, N.; Russell, A.; Pierce, D. W.; Jia, Z.; McCormick, C. D.; Hartman, J.; Sakowicz, R.; Pollard, T. D. Characterization of two classes of small molecule inhibitors of Arp2/3 complex Nature 2009, 460, 1031-1034
34. Wu, J.; Yu, L.; Yang, F.; Li, J.; Wang, P.; Zhou, W.; Qin, L.; Li, Y.; Luo, J.; Yi, Z.; Liu, M.; Chen, Y. Optimization of 2-(3-(arylalkyl amino carbonyl)phenyl)-3-(2-methoxyphenyl)-4-thiazolidinone derivatives as potent antitumor growth and metastasis agents Eur. J. Med. Chem. 2014, 80c, 340-351
35. Grolla, A. A.; Podesta, V.; Chini, M. G.; Di Micco, S.; Vallario, A.; Genazzani, A. A.; Canonico, P. L.; Bifulco, G.; Tron, G. C.; Sorba, G.; Pirali, T. Synthesis, biological evaluation, and molecular docking of Ugi products containing a zinc-chelating moiety as novel inhibitors of histone deacetylases J. Med. Chem. 2009, 52, 2776-2785
36. Miller, T. A.; Witter, D. J.; Belvedere, S. Diamine and iminodiacetic acid hydroxamic acid derivatives. Patent WO2005/053610 A2, 2005.
37. Terracciano, S.; Chini, M. G.; Bifulco, G.; D'Amico, E.; Marzocco, S.; Riccio, R.; Bruno, I. Synthesis of new mono and bis amides projected as potential histone deacetylase (HDAC) inhibitors Tetrahedron 2010, 66, 2520-2528
38. Terracciano, S.; Chini, M. G.; Riccio, R.; Bruno, I.; Bifulco, G. Design, synthesis, and biological activity of hydroxamic tertiary amines as histone deacetylase inhibitors ChemMedChem. 2012, 7, 694-702
39. Chen, Y.; Lopez-Sanchez, M.; Savoy, D. N.; Billadeau, D. D.; Dow, G. S.; Kozikowski, A. P. A series of potent and selective, triazolylphenyl-based histone deacetylases inhibitors with activity against pancreatic cancer cells and Plasmodium falciparum J. Med. Chem. 2008, 51, 3437-3448
40. Huang, H.; La, D. S.; Cheng, A. C.; Whittington, D. A.; Patel, V. F.; Chen, K.; Dineen, T. A.; Epstein, O.; Graceffa, R.; Hickman, D.; Kiang, Y. H.; Louie, S.; Luo, Y.; Wahl, R. C.; Wen, P. H.; Wood, S.; Fremeau, R. T., Jr. Structure- and property-based design of aminooxazoline xanthenes as selective, orally efficacious, and CNS penetrable BACE inhibitors for the treatment of Alzheimer's disease J. Med. Chem. 2012, 55, 9156-9169
41. Xin, Q.; Fan, H.; Guo, B.; He, H.; Gao, S.; Wang, H.; Huang, Y.; Yang, Y. Design, synthesis, and structure-activity relationship studies of highly potent novel benzoxazinyl-oxazolidinone antibacterial agents J. Med. Chem. 2011, 54, 7493-7502
42. Gryder, B. E.; Rood, M. K.; Johnson, K. A.; Patil, V.; Raftery, E. D.; Yao, L. P.; Rice, M.; Azizi, B.; Doyle, D. F.; Oyelere, A. K. Histone deacetylase inhibitors equipped with estrogen receptor modulation activity J. Med. Chem. 2013, 56, 5782-5796
43. Feng, W.; Zhang, B.; Cai, D.; Zou, X. Therapeutic potential of histone deacetylase inhibitors in pancreatic cancer Cancer Lett. 2014, 347, 183-190
44. Siegel, R.; Ma, J.; Zou, Z.; Jemal, A. Cancer statistics, 2014 CA Cancer J. Clin. 2014, 64, 9-29
45. Fraga, M. F.; Ballestar, E.; Villar-Garea, A.; Boix-Chornet, M.; Espada, J.; Schotta, G.; Bonaldi, T.; Haydon, C.; Ropero, S.; Petrie, K.; Iyer, N. G.; Perez-Rosado, A.; Calvo, E.; Lopez, J. A.; Cano, A.; Calasanz, M. J.; Colomer, D.; Piris, M. A.; Ahn, N.; Imhof, A.; Caldas, C.; Jenuwein, T.; Esteller, M. Loss of acetylation at Lys16 and trimethylation at Lys20 of histone H4 is a common hallmark of human cancer Nat. Genet. 2005, 37, 391-400
46. Deakin, N. O.; Turner, C. E. Distinct roles for paxillin and Hic-5 in regulating breast cancer cell morphology, invasion, and metastasis Mol. Biol. Cell 2011, 22, 327-341
47. Sen, A.; O'Malley, K.; Wang, Z.; Raj, G. V.; Defranco, D. B.; Hammes, S. R. Paxillin regulates androgen- and epidermal growth factor-induced MAPK signaling and cell proliferation in prostate cancer cells J. Biol. Chem. 2010, 285, 28787-28795
48. Yu, M.; Bardia, A.; Wittner, B. S.; Stott, S. L.; Smas, M. E.; Ting, D. T.; Isakoff, S. J.; Ciciliano, J. C.; Wells, M. N.; Shah, A. M.; Concannon, K. F.; Donaldson, M. C.; Sequist, L. V.; Brachtel, E.; Sgroi, D.; Baselga, J.; Ramaswamy, S.; Toner, M.; Haber, D. A.; Maheswaran, S. Circulating breast tumor cells exhibit dynamic changes in epithelial and mesenchymal composition Science 2013, 339, 580-584
49. Zhang, X.; Yuan, Z.; Zhang, Y.; Yong, S.; Salas-Burgos, A.; Koomen, J.; Olashaw, N.; Parsons, J. T.; Yang, X. J.; Dent, S. R.; Yao, T. P.; Lane, W. S.; Seto, E. HDAC6 modulates cell motility by altering the acetylation level of cortactin Mol. Cell 2007, 27, 197-213
50. Stamenkovic, I. Matrix metalloproteinases in tumor invasion and metastasis Semin. Cancer Biol. 2000, 10, 415-433
51. Metsugi, Y.; Miyaji, Y.; Ogawara, K.; Higaki, K.; Kimura, T. Appearance of double peaks in plasma concentration-time profile after oral administration depends on gastric emptying profile and weight function Pharm. Res. 2008, 25, 886-895