Zhang Lei, Zhang Jian, Jiang Qixiao, Zhang Li, Song Weiguo
a Department of Medicinal Chemistry, School of Pharmacy , Weifang Medical University , Weifang , Shandong , China.
b School of Pharmacy , Qingdao University , Qingdao , Shandong , China.
J Enzyme Inhib Med Chem. 2018 Dec;33(1):714-721. doi: 10.1080/14756366.2017.1417274.
Zinc binding groups (ZBGs) play a crucial role in targeting histone deacetylase inhibitors (HDACIs) to the active site of histone deacetylases (HDACs), thus determining the potency of HDACIs. Due to the high affinity to the zinc ion, hydroxamic acid is the most commonly used ZBG in the structure of HDACs. An alternative ZBG is benzamide group, which features excellent inhibitory selectivity for class I HDACs. Various ZBGs have been designed and tested to improve the activity and selectivity of HDACIs, and to overcome the pharmacokinetic limitations of current HDACIs. Herein, different kinds of ZBGs are reviewed and their features have been discussed for further design of HDACIs.
锌结合基团（ZBGs）在将组蛋白去乙酰化酶抑制剂（HDACIs）靶向至组蛋白去乙酰化酶（HDACs）的活性位点方面发挥着关键作用，从而决定了HDACIs的效力。由于对锌离子具有高亲和力，异羟肟酸是HDACs结构中最常用的ZBG。另一种ZBG是苯甲酰胺基团，其对I类HDACs具有出色的抑制选择性。已经设计并测试了各种ZBG，以提高HDACIs的活性和选择性，并克服当前HDACIs的药代动力学限制。在此，对不同种类的ZBG进行了综述，并讨论了它们的特征，以便进一步设计HDACIs。
