School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China.
Bioorg Med Chem Lett. 2009 Nov 15;19(22):6284-8. doi: 10.1016/j.bmcl.2009.09.100. Epub 2009 Sep 29.
Ongoing effort to gather further knowledge about the structural requirements on histone deacetylase inhibitors led to the synthesis of novel N-hydroxybenzamide-based HDAC inhibitors 1a-o, introducing branched hydrophobic groups at the capping group, and their inhibition activity against HDACs and anti-proliferation activity in four tumor cell lines were determined. Compounds 1j-o were further tested against recombinant human HDAC1 and HDAC4 to evaluate their selectivity profile. This work further suggests that the chemical nature of the capping group is critical for subtle discrimination between the class I and the class II HDAC isoforms.
为了进一步了解组蛋白去乙酰化酶抑制剂的结构要求，我们一直在努力，这导致了新型 N-羟基苯甲酰胺基 HDAC 抑制剂 1a-o 的合成，在盖帽基团上引入支化疏水基团，并测定了它们对 HDAC 的抑制活性和对四种肿瘤细胞系的抗增殖活性。进一步测试了化合物 1j-o 对重组人 HDAC1 和 HDAC4 的抑制活性，以评估它们的选择性。这项工作进一步表明，盖帽基团的化学性质对于 I 类和 II 类 HDAC 同工酶之间的细微区分至关重要。
