%0 Journal Article
%T Design, synthesis and biological evaluation of 4-piperidin-4-yltriazole derivatives as novel histone deacetylase inhibitors.
%A Gao JJ
%A Han YT
%A Luan YP
%A Miao H
%A Mou ZS
%A Su L
%A Wang BL
%A Zhang L
%J BioScienceTrends
%D 2019
%R BioScience Trends. 2019 ;13(2):197-203. (DOI: 10.5582/bst.2019.01055)
%X SUMMARY: 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 ¦ÌM. 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. Key Words: Histone deacetylase, isoform, selective, inhibitor, anti-tumor Full Text: PDF(886KB
%U http://www.biosciencetrends.com/getabstract.php?id=1702