BioScience Trends. 2019;13(2):197-203. (DOI: 10.5582/bst.2019.01055)

Design, synthesis and biological evaluation of 4-piperidin-4-yltriazole derivatives as novel histone deacetylase inhibitors.

Miao H, Gao JJ, Mou ZS, Wang BL, Zhang L, Su L, Han YT, Luan YP


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.

KEYWORDS: Histone deacetylase, isoform, selective, inhibitor, anti-tumor

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