Histone deacetylases (HDACs) are proteases that can catalyze the deacetylation of histones to inhibit gene transcription. Since mutations and/or aberrant expression of various HDACs are frequently associated with human diseases, particularly cancers, HDACs are important therapeutic targets for many human tumors. However, there are still relatively few studies on HDAC small molecule fluorescent probes. Herein, we designed and synthesized a class of environment-sensitive fluorescent inhibitors with a switch mechanism to study HDAC activity. In vitro, the enzyme inhibition activity of compound 6b was comparable to the positive control drug SAHA, and it presented suitable imaging in living cells and tumor-tissue slices. This environment-sensitive fluorescent inhibitor provides a new idea for the diagnosis and treatment of HDACs-related diseases.

中文翻译：

---

环境敏感的组蛋白脱乙酰基酶荧光抑制剂。

组蛋白脱乙酰基酶（HDACs）是可以催化组蛋白脱乙酰基以抑制基因转录的蛋白酶。由于各种HDAC的突变和/或异常表达经常与人类疾病，特别是癌症相关，因此HDAC是许多人类肿瘤的重要治疗靶标。但是，关于HDAC小分子荧光探针的研究仍然相对较少。在这里，我们设计和合成了一类具有开关机制的环境敏感型荧光抑制剂，以研究HDAC的活性。在体外，化合物6b的酶抑制活性与阳性对照药物SAHA相当，并且在活细胞和肿瘤组织切片中显示出合适的成像效果。这种对环境敏感的荧光抑制剂为HDACs相关疾病的诊断和治疗提供了新思路。