Histone deacetylase inhibitors (HDACIs) are effective small molecules in the treatment of human cancers. In our continuing efforts to develop novel N-hydroxyterephthalamide-based HDACIs, herein we report the design and development of a new class of N-hydroxybenzamide-based HDACIs. In this new class of analogs, we inserted an ethylene moiety in the linker and used indole as a part of the Y-shaped cap group. Biological characterization identified compounds 4o, 4p, 4q and 4t to show improved HDAC inhibition, while no isoform selectivity for HDACs was observed. These compounds also exhibited improved anti-proliferative activity against multiple cancer cell lines when compared to their parent compound and positive control SAHA.

组蛋白脱乙酰基酶抑制剂（HDACIs）是治疗人类癌症的有效小分子。在我们继续努力开发新的ñ基于-hydroxyterephthalamide-HDACIs，在此我们报道了一类新的设计和开发ñ为主-hydroxybenzamide HDACIs。在这一类新的类似物中，我们在连接子中插入了一个乙烯部分，并将吲哚用作Y形帽基的一部分。生物学鉴定鉴定出化合物4o，4p，4q和4t显示出改善的HDAC抑制作用，而未观察到HDAC的同工型选择性。与它们的母体化合物和阳性对照SAHA相比，这些化合物还对多种癌细胞系表现出改善的抗增殖活性。