Dept. of Chemistry, School of Life Sciences, University of Sussex, Falmer, Brighton BN1 9QJ, East Sussex, UK.
Bioorg Med Chem Lett. 2013 Jun 1;23(11):3346-8. doi: 10.1016/j.bmcl.2013.03.084. Epub 2013 Apr 2.
We have synthesized a β-cyclodextrin (βCD)-capped histone deacetylase (HDAC) inhibitor 3 containing an alkyl linker and a zinc-binding hydroxamic acid motif. Biological evaluation (HDAC inhibition studies) of 3 enabled us to establish the effect of replacing an aryl cap (in SAHA (vorinostat,)) 1 by a large saccharidic scaffold "cap". HDAC inhibition was observed for 3, to a lesser extent than SAHA, and rationalized by molecular docking into the active site of HDAC8. However, compound 3 displayed no cellular activity.
我们合成了一种β-环糊精（βCD）封端的组蛋白去乙酰化酶（HDAC）抑制剂 3，其中含有一个烷基连接子和一个锌结合的羟肟酸基序。3 的生物学评价（HDAC 抑制研究）使我们能够确定用大的糖基支架“帽”取代芳基帽（在 SAHA（伏立诺他）中）1 的效果。与 SAHA 相比，3 的 HDAC 抑制作用较弱，并且通过分子对接进入 HDAC8 的活性位点得到了合理的解释。然而，化合物 3 没有表现出细胞活性。
