- 著者
- He Miao Jianjun Gao Zishuo Mou Baolei Wang Li Zhang Li Su Yantao Han Yepeng Luan
- 出版者
- International Research and Cooperation Association for Bio & Socio-Sciences Advancement
- 雑誌
- BioScience Trends (ISSN:18817815)
- 巻号頁・発行日
- pp.2019.01055, (Released:2019-04-25)
- 参考文献数
- 31
- 被引用文献数
- 7
Histone deacetylase is an important member of epigenetics and a well validated target for anti-cancer drug discovery. In this study, we designed and synthesized a series of twenty-one novel hydroxamic acid-based histone deacetylase inhibitors with 4-piperidin-4-yl-triazole as the core skeleton. Most target compounds displayed excellent inhibition rates toward histone deacetylases at the concentration of 1 μM. Among them, the inhibition rates of two compounds MH1-18 and MH1-21 exceeded 90%. Furthermore, these two compounds selectively inhibited the activity of histone deacetylase 6 with low IC50 values. The high potency of them toward histone deacetylase 6 was rationalized by molecular docking studies. We found that MH1-18 and MH1-21 moderately inhibited the proliferation of four human cancer cell lines SGC-7901, NCI-H226, MCF-7, and HL-60. However, MH1-21 showed potent efficacy in suppressing the migration of MCF-7 cells. Results obtained in the current study shed light on designing potent HDAC6 inhibitors as anti-cancer agents.