Amin Sk Abdul, Adhikari Nilanjan, Jha Tarun
Natural Science Laboratory, Department of Pharmaceutical Technology, Division of Medicinal & Pharmaceutical Chemistry, PO Box 17020, Jadavpur University, Kolkata 700032, West Bengal, India.
Future Med Chem. 2017 Dec;9(18):2211-2237. doi: 10.4155/fmc-2017-0130. Epub 2017 Nov 28.
The pan-histone deacetylase (HDAC) inhibitors comprise a fish-like structural orientation where hydrophobic aryl- and zinc-binding groups act as head and tail, respectively of a fish. The linker moiety correlates the body of the fish linking head and tail groups. Despite these pan-HDAC inhibitors, selective HDAC-8 inhibitors are still in demand as a safe remedy. HDAC-8 is involved in invasion and metastasis in cancer. This review deals with the rationale behind HDAC-8 inhibitory activity and selectivity along with detailed structure-activity relationships of diverse hydroxamate-based HDAC-8 inhibitors. HDAC-8 inhibitory potency may be increased by modifying the fish-like pharmacophoric features of such type of pan-HDAC inhibitors. This review may provide a preliminary basis to design and optimize new lead molecules with higher HDAC-8 inhibitory activity. This work may surely enlighten in providing useful information in the field of target-specific anticancer therapy.
泛组蛋白去乙酰化酶（HDAC）抑制剂具有类似鱼的结构取向，其中疏水性芳基结合基团和锌结合基团分别作为鱼的头部和尾部。连接部分则相当于鱼的身体，连接着头尾基团。尽管有这些泛HDAC抑制剂，但作为一种安全的治疗方法，选择性HDAC-8抑制剂仍然很有需求。HDAC-8与癌症的侵袭和转移有关。本综述探讨了HDAC-8抑制活性和选择性背后的原理，以及各种基于异羟肟酸的HDAC-8抑制剂的详细构效关系。通过修饰此类泛HDAC抑制剂的类鱼药效特征，可以提高HDAC-8的抑制效力。本综述可为设计和优化具有更高HDAC-8抑制活性的新先导分子提供初步依据。这项工作肯定会为靶向特异性抗癌治疗领域提供有用信息提供启示。
