Chemistry of Heterocyclic Compounds

, Volume 51, Issue 7, pp 647–657 | Cite as

Synthesis and biological evaluation of aziridin-1-yl oxime-based vorinostat analogs as anticancer agents

  • Anna Nikitjuka
  • Irina Shestakova
  • Nadezhda Romanchikova
  • Aigars Jirgensons
Article
  • 319 Downloads
The suberoyl anilide hydroxamic acid (vorinostat) analogs with the aziridin-1-yl oxime moiety as a possible metal chelating functionality have been synthesized. Their biological activity and stability under physiological conditions have been evaluated. Although some of the synthesized compounds demonstrated high antiproliferative activity against human HT1080 fibrosarcoma (HT1080, IC50 0.3–7.7 μM) comparable to vorinostat (HT1080, IC50 2.4 μM), they showed only weak histone deacetylase inhibition activity in HeLa cell line extracts.

Keywords

aldoxime aziridin-1-yl oxime histone deacetylase hydroximoyl chloride suberoyl anilide hydroxamic acid cytotoxic activity 

References

  1. 1.
    Oger, F.; Lecorgne, A.; Sala, E.; Nardese, V.; Dernay, F.; Chevance, S.; Desravines, D. C.; Aleksandrova, N.; Le Guével, R.; Lorenzi, S.; Beccari, A. R.; Barath, P.; Hart, D. J.; Bondon, A.; Carretoni, D.; Simonneaux, G.; Salbert, G. J. Med. Chem. 2010, 53, 1937.CrossRefGoogle Scholar
  2. 2.
    Nikitjuka, A.; Jirgensons, A. Chem. Hetereocycl. Compd. 2013, 49, 1544. [Khim. Geterotskl. Soedin. 2013, 1669.]Google Scholar
  3. 3.
    Grigorjeva, A.; Jirgensons, A.; Domracheva, I.; Yashchenko, E.; Shestakova, I.; Andrianov, V.; Kalvinsh, I. Chem. Hetereocycl. Compd. 2009, 45, 161. [Khim. Geterotskl. Soedin. 2009, 203.]Google Scholar
  4. 4.
    Mai, A.; Esposito, M.; Sbardella, G.; Massa, S. Org. Prep. Proced. Int. 2001, 33, 391.CrossRefGoogle Scholar
  5. 5.
    Bosone, E.; Farina, P.; Guazzi, G.; Innocenti, S.; Marotta, V.; Valcavi, U. Synthesis 1983, 942.Google Scholar
  6. 6.
    Choi, S. E.; Weerasinghe, S. V. W.; Pflum, M. K. H. Biorg. Med. Chem. Lett. 2011, 21, 6139.CrossRefGoogle Scholar
  7. 7.
    Liu K.-C.; Shelton B. R.; Howe R. K. J. Org. Chem. 1980, 45, 3916.CrossRefGoogle Scholar
  8. 8.
    Gucma, M.; Gołebiewski, W. M. Synthesis 2008, 13, 1997.Google Scholar
  9. 9.
    Fang, Y.-Q.; Jacobsen, E. N. J. Am. Chem. Soc. 2008, 130, 5660.CrossRefGoogle Scholar
  10. 10.
    Ghosh, S.; Lobera, M.; Pohlhaus, D. T.; Trump, R. P.; Zhang, C.; Zuercher, W. WO Patent 2013066836.Google Scholar
  11. 11.
    Dai, Y.; Guo, Y.; Curtin, M. L.; Li, J.; Pease, L. J.; Guo, J.; Marcotte, P. A.; Glaser, K. B.; Davidsen, S. K.; Michaelides, M. R. Bioorg. Med. Chem. Lett. 2003, 13, 3817.CrossRefGoogle Scholar
  12. 12.
    Regulation (EC) No 1272/2008 on classification, labelling, and packaging of substances and mixtures, amending and repealing, Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006. http://eur-lex.europa.eu/LexUriServ/LexUriServ.do?uri=OJ:L:2008:353:0001:1355:EN:PDF
  13. 13.
    Stokes, W. S.; Casati, S.; Strickland, J.; Paris, M. In Current Protocols in Toxicology; John Wiley & Sons: New York, 2008, Vol. 36, p. 20.4.1.Google Scholar
  14. 14.
    Canonica, S.; Ferrari, M.; Sisti, M. Org. Prep. Proced. Int. 1989, 21, 253.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Anna Nikitjuka
    • 1
  • Irina Shestakova
    • 1
  • Nadezhda Romanchikova
    • 1
  • Aigars Jirgensons
    • 1
  1. 1.Latvian Institute of Organic SynthesisRigaLatvia

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