Histone deacetylases (HDACs) has proved to be promising target for the development of antitumor drugs. In this study, we reported the design and synthesis of a class of novel hydroxamate-based bis-substituted aromatic amide HDAC inhibitors with 1,2,4-oxadiazole core. Most newly synthesized compounds displayed excellent HDAC1 inhibitory effects and significant anti-proliferative activities. Among them, compounds 11a and 11c increased acetylation of histone H3 and H4 in dose-dependent manner. Furthermore, 11a and 11c remarkably induced apoptosis in HepG2 cancer cells. Finally, the high potency of compound 11a was rationalized by molecular docking studies.

组蛋白脱乙酰基酶（HDAC）已被证明是抗肿瘤药物开发的有希望的目标。在这项研究中，我们报道了具有1,2,4-恶二唑核心的一类新型基于异羟肟酸酯的双取代芳族酰胺HDAC抑制剂的设计和合成。大多数新合成的化合物显示出出色的HDAC1抑制作用和显着的抗增殖活性。其中，化合物11a和11c以剂量依赖性方式增加组蛋白H3和H4的乙酰化。此外，11a和11c显着诱导了HepG2癌细胞的凋亡。最后，化合物11a的高效能通过分子对接研究得以合理化。