Synthesis of a novel series of benzylether-containing cinnamoyl derivatives as histone deacetylase inhibitors

Abstract

Histone deacetylases (HDACs) play an important role in gene transcription, cellular proliferation, apoptosis, and tumorigenesis. A novel series of benzylether-containing cinnamoyl derivatives were designed and synthesized as inhibitors of histone deacetylases (HDACs). Most of these compounds possessed inhibitory activity against the enzymes with IC₅₀ values as low as 30 μM. In addition, compounds 4d (IC₅₀ = 11.1 μM) and 4n (IC₅₀ = 7.7 μM) exhibited high antiproliferative activity against tumor cell growth and effectively induced cell cycle arrest.

Keywords::

• Histone deacetylases
• benzylether
• cinnamoyl derivatives
• inhibitors

Acknowledgments

This work was supported by the National “863” Foundation of China (Grant No. 2007AA02Z314). We thank Huawei Zhu for his contributions to the work of binding analysis using software Sybyl 7.0, and Xuejian Wang for his contributions to the work of MTT assay.

Declaration of interest: The authors report no conflicts of interest.