Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 250012 Ji'nan, Shandong, PR China.
Eur J Med Chem. 2009 Nov;44(11):4470-6. doi: 10.1016/j.ejmech.2009.06.010. Epub 2009 Jun 17.
A novel series of N-hydroxy-4-(3-phenylpropanamido)benzamide (HPPB) derivatives comprising N-hydroxybenzamide group as zinc-chelating moiety were designed, synthesized and evaluated for their ability to inhibit histone deacetylases. These compounds possessed inhibitory activity against the enzymes with IC(50) values as low as 4.0 microM. Among them, the thiophene substituted derivative 5j (IC(50)=0.3 microM) and benzo[d][1,3]dioxole derivative 5t (IC(50)=0.4 microM) exhibited good antiproliferative activity against the growth of human colon carcinoma cell line HCT116 and non-small cell lung cancer cell (NSCLC) line A549. In addition, they were found to potently induce cell-cycle arrest at G2 phase.
设计、合成了一系列新型 N-羟基-4-(3-苯丙酰胺基)苯甲酰胺（HPPB）衍生物，这些化合物包含作为锌螯合部分的 N-羟基苯甲酰胺基团，并评估了它们抑制组蛋白去乙酰化酶的能力。这些化合物对酶具有抑制活性，IC（50）值低至 4.0 μM。其中，噻吩取代的衍生物 5j（IC（50）=0.3 μM）和苯并[d][1,3]二恶唑衍生物 5t（IC（50）=0.4 μM）对人结肠癌细胞系 HCT116 和非小细胞肺癌细胞（NSCLC）系 A549 的生长表现出良好的抗增殖活性。此外，它们被发现能够强有力地诱导细胞周期停滞在 G2 期。
