Amino Acids

, Volume 46, Issue 10, pp 2435–2444 | Cite as

Design and synthesis of mono and bicyclic tetrapeptides thioester as potent inhibitor of histone deacetylases

  • Md. Ashraful HoqueEmail author
  • Md. Shahidul Islam
  • Md. Nurul Islam
  • Tamaki Kato
  • Norikazu Nishino
  • Akihiro Ito
  • Minoru Yoshida
Original Article


Inhibitors of histone deacetylases (HDACs) are a promising class of anticancer agents that have an effect on gene regulation. The naturally occurring cyclic depsipeptide FK228 containing disulfide and Largazole possessing thioester functionalities act as pro-drugs and share the same HDAC inhibition mechanism in cell. Inspired from these facts, we have reported bicyclic tetrapeptide disulfide HDAC inhibitors resembling FK228 with potent activity and enhanced selectivity. In the present study, we report the design and synthesis of several mono and bicyclic tetrapeptide thioester HDAC inhibitors that share the inhibition mechanism similar to Largazole. Most of the compounds showed HDAC1 and HDAC4 inhibition and p21 promoting activity in nanomolar ranges. Among these the monocyclic peptides 1, 2 and bicyclic peptide, 4 are notable demanding more advanced research to be promising anticancer drug candidates.


Histone deacetylase inhibitors Depsipeptide Largazole Bicyclic tetrapeptides 


Conflict of interest

The authors declare that they have no conflict of interest.


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Copyright information

© Springer-Verlag Wien 2014

Authors and Affiliations

  • Md. Ashraful Hoque
    • 1
    • 2
    • 3
    Email author
  • Md. Shahidul Islam
    • 3
    • 4
  • Md. Nurul Islam
    • 3
    • 4
  • Tamaki Kato
    • 3
  • Norikazu Nishino
    • 3
  • Akihiro Ito
    • 5
  • Minoru Yoshida
    • 5
  1. 1.Department of Chemistry, Faculty of ScienceUniversiti Putra MalaysiaSerdangMalaysia
  2. 2.Department of Biochemistry and Molecular Biology, Faculty of ScienceUniversity of RajshahiRajshahiBangladesh
  3. 3.Graduate School of Life Science and Systems EngineeringKyushu Institute of TechnologyKitakyushuJapan
  4. 4.Department of Chemistry, Faculty of ScienceUniversity of RajshahiRajshahiBangladesh
  5. 5.RIKENSaitamaJapan

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