Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
권호 표지
DOI QR코드

DOI QR Code

Synthesis of Novel N-(2-Hydroxyphenyl)arylsulfonamides as Selective HDAC Inhibitory and Cytotoxic Agents

  • Kim, Jungsu (Laboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University) ;
  • Chun, Pusoon (College of Pharmacy, Inje University) ;
  • Moon, Hyung Ryong (Laboratory of Medicinal Chemistry, College of Pharmacy, Pusan National University)
  • Received : 2013.02.12
  • Accepted : 2013.02.26
  • Published : 2013.05.20
Download PDF
⟨ Previous Next ⟩

Abstract

Based on the finding that the 2-aminobenzamido group of MS-275 plays a crucial role in inhibiting HDACs through chelation of zinc existing at the active site of HDAC enzymes, novel N-(2-hydroxyphenyl)arylsulfonamide derivatives were synthesized for their potential ability to inhibit HDACs and evaluated for anticancer activity against human breast cancer cell line (MCF-7). Although the synthesized arylsulfonamides have failed to significantly inhibit total HDACs activity, phenyl carbamate-linked arylsulfonamide 10 and benzyl thiocarbamate-linked arylsulfonamide 15 exhibited good anticancer activities, which were only 4.3- and 3.6-fold lower anticancer activities, respectively, than MS-275 that is undergoing phase II clinical trials. These results suggest that these compounds may act as a selective HDAC inhibitor and probably N-(2-hydroxyphenyl) sulfamoyl group may play an important role in interacting with HDAC enzymes through chelation of zinc ion.

Keywords

References

  1. Wu, J.; Grunstein, M. Trends Biochem. Sci. 2000, 25, 619. https://doi.org/10.1016/S0968-0004(00)01718-7
  2. Luger, K.; Mader, A. W.; Richmond, R. K.; Sargent, D. F.; Richmond, T. J. Nature 1997, 389, 251. https://doi.org/10.1038/38444
  3. Marmorstein, R.; Roth, S. Y. Curr. Opin. Genet. Dev. 2001, 11, 155. https://doi.org/10.1016/S0959-437X(00)00173-8
  4. Hassig, C. A.; Schreiber, S. L. Curr. Opin. Chem. Biol. 1997, 1, 300. https://doi.org/10.1016/S1367-5931(97)80066-X
  5. Johnstone, R. W. Nat. Rev. Drug Discov. 2002, 1, 287. https://doi.org/10.1038/nrd772
  6. Thiagalingam, S.; Cheng, K.-H.; Lee, H. J.; Mineva, N.; Thiagalingam, A.; Ponte, J. F. Ann. N. Y. Acad. Sci. 2003, 983, 84. https://doi.org/10.1111/j.1749-6632.2003.tb05964.x
  7. Roth, S. Y.; Denu, J. M.; Allis, C. D. Ann. Rev. Biochem. 2001, 70, 81. https://doi.org/10.1146/annurev.biochem.70.1.81
  8. Bolden, J. E.; Peart, M. J.; Johnstone, R. W. Nat. Rev. Drug Discov. 2006, 5, 769. https://doi.org/10.1038/nrd2133
  9. Marks, P. A.; Rifkind, R. A.; Richon, V. M.; Breslow, R.; Miller, T.; Kelly, W. K. Nat. Rev. Cancer. 2001, 1, 194. https://doi.org/10.1038/35106079
  10. Lindemann, R. K.; Gabrielli, B.; Johnstone, R. W. Cell Cycle 2004, 3, 777. https://doi.org/10.4161/cc.3.6.927
  11. Suzuki, T.; Ando, T.; Tsuchiya, K.; Fukazawa, N. J. Med. Chem. 1999, 42, 3001. https://doi.org/10.1021/jm980565u
  12. Saito, A.; Yamashita, T.; Mariko, Y.; Nosaka, Y.; Tsuchiya, K.; Ando, T.; Suzuki, T.; Tsuruo, T.; Nakanishi, O. Proc. Natl. Acad. Sci. 1999, 96, 4592. https://doi.org/10.1073/pnas.96.8.4592
  13. Meinke, P. T.; Liberator, P. Curr. Med. Chem. 2001, 8, 211. https://doi.org/10.2174/0929867013373787
  14. Bouchain, G.; Delorme, D. Curr. Med. Chem. 2003, 10, 2359. https://doi.org/10.2174/0929867033456585
  15. Hess-Stumpp, H.; Bracker, T. U.; Henderson, D.; Politz, O. Int. J. Biochem. Cell Biol. 2007, 39, 1388. https://doi.org/10.1016/j.biocel.2007.02.009
  16. Wang, D.-F.; Helquist, P.; Wiech, N. L.; Wiest, O. J. Med. Chem. 2005, 48, 6936. https://doi.org/10.1021/jm0505011
  17. Michaelides, M. R.; Dellaria, J. F.; Gong, J.; Holms, J. H.; Bouska, J. J.; Stacey, J.; Wada, C. K.; Heyman, H. R.; Curtin, M. L.; Guo, Y.; Goodfellow, C. L.; Elmore, I. B.; Albert, D. H.; Magoc, T. J.; Marcotte, P. A.; Morgan, D. W.; Davidsen, S. K. Bioorg. Med. Chem. Lett. 2001, 11, 1553. https://doi.org/10.1016/S0960-894X(01)00031-2
  18. Curtin, M.; Glaser, K. Curr. Med. Chem. 2003, 10, 2373. https://doi.org/10.2174/0929867033456576
  19. Nagaoka, Y.; Maeda, T.; Kawai, Y.; Nakashima, D.; Oikawa, T.; Shimoke, K.; Ikeuchi, T.; Kuwajima, H.; Uesato, S. Eur. J. Med. Chem. 2006, 41, 697. https://doi.org/10.1016/j.ejmech.2006.02.002