Department of Medicinal Chemistry, Key aboratory of Chemical Biology (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China.
Department of Medicinal Chemistry, Key aboratory of Chemical Biology (MOE), School of Pharmacy, Shandong University, Jinan, Shandong 250012, China.
Bioorg Med Chem Lett. 2020 Jun 1;30(11):127128. doi: 10.1016/j.bmcl.2020.127128. Epub 2020 Mar 20.
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.
组蛋白去乙酰化酶（HDACs）是一类蛋白酶，可以催化组蛋白的去乙酰化，从而抑制基因转录。由于各种 HDAC 的突变和/或异常表达常常与人类疾病，尤其是癌症有关，因此 HDAC 是许多人类肿瘤的重要治疗靶点。然而，目前关于 HDAC 小分子荧光探针的研究仍然相对较少。在此，我们设计并合成了一类具有开关机制的环境敏感型荧光抑制剂，用于研究 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呈现出合适的成像效果。这种环境敏感型荧光抑制剂为 HDAC 相关疾病的诊断和治疗提供了新的思路。
