Design, synthesis and primary activity assay of tripeptidomimetics as histone deacetylase inhibitors with linear linker and branched cap group.

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Zhang Y, Feng J, Jia Y, Xu Y, Liu C, Fang H, Xu W

Design, synthesis and primary activity assay of tripeptidomimetics as histone deacetylase inhibitors with linear linker and branched cap group.

Eur J Med Chem. 2011 Nov;46(11):5387-97. doi: 10.1016/j.ejmech.2011.08.045. Epub 2011 Sep 8.

PubMed ID

21924799 [ View in PubMed

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Abstract

A novel series of tripeptidomimetics with spiro ring containing sulfur atoms as cap group and linear carbochain as linker was designed and synthesized as HDACs inhibitors. Several compounds possessed more potent HDAC8 inhibitory activity than clinically used drug SAHA, although their HDAC1 inhibitory activities and anti-proliferative activities against human breast cancer cell lines (MCF-7, MDA-MB-231) and prostate cancer cell line (PC-3) were not satisfactory. Among them, compounds 11l and 11k showed excellent potency against HDAC8 (IC(50) values were 0.021 +/- 0.004 muM and 0.035 +/- 0.007 muM, respectively, whereas SAHA was 0.70 +/- 0.12 muM), and good selectivity over HDAC1. Up to now, few hydroxamic acid derivatives with linear linker were reported to possess HDAC8 selectivity over HDAC1.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Vorinostat	Histone deacetylase 1	IC 50 (nM)	44	N/A	N/A	Details