Design and synthesis of CHAP31, trapoxin B and HC-toxin based bicyclic tetrapeptides disulfide as potent histone deacetylase inhibitors

Md Ashraful Hoque; Md Nurul Islam; Md Shahidul Islam; Tamaki Kato; Norikazu Nishino; Akihiro Ito; Minoru Yoshida

doi:10.1016/j.bmc.2014.06.029

Design and synthesis of CHAP31, trapoxin B and HC-toxin based bicyclic tetrapeptides disulfide as potent histone deacetylase inhibitors

Bioorg Med Chem. 2014 Aug 1;22(15):3850-5. doi: 10.1016/j.bmc.2014.06.029. Epub 2014 Jun 25.

Authors

Md Ashraful Hoque¹, Md Nurul Islam², Md Shahidul Islam², Tamaki Kato³, Norikazu Nishino³, Akihiro Ito⁴, Minoru Yoshida⁴

Affiliations

¹ Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan; Department of Biochemistry and Molecular Biology, Faculty of Science, University of Rajshahi, Rajshahi 6205, Bangladesh. Electronic address: ashraf_bio2003@yahoo.com.
² Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan; Department of Chemistry, Faculty of Science, University of Rajshahi, Rajshahi 6205, Bangladesh.
³ Graduate School of Life Science and Systems Engineering, Kyushu Institute of Technology, Kitakyushu 808-0196, Japan.
⁴ Chemical Genetics Laboratory/Chemical Genomics Research Group, RIKEN Advanced Science Institute, Saitama 351-0198, Japan.

PMID: 24997578
DOI: 10.1016/j.bmc.2014.06.029

Abstract

The naturally occurring cyclic depsipeptide, FK228 inhibits histone deacetylase (HDAC) enzymes after reductive cleavage of intra-molecular disulfide bond. One of the sulfhydryl groups produced in the reduction interacts with zinc atom that involved in the catalytic mechanism of type 1 and 2 HDACs such as HDAC1, HDAC4, and HDAC6. In the present study, we describe the development of CHAP31, trapoxin B and HC-toxin based cyclic tetrapeptides with intra-molecular disulfide bond as HDAC inhibitors. The bicyclic tetrapeptides disulfide showed potent HDAC1 and HDAC4 inhibition and p21 promoting activity.

Keywords: Bicyclic tetrapeptides; Depsipeptide; FK228; Histone deacetylase inhibitors; Sulfhydryl group.

Publication types

Research Support, Non-U.S. Gov't
Retracted Publication