设计、合成及 8-取代喹啉-2-甲酰胺衍生物的生物活性评价作为新型组蛋白去乙酰化酶（HDAC）抑制剂。
Design, synthesis and bioactivity evaluations of 8-substituted-quinoline-2-carboxamide derivatives as novel histone deacetylase (HDAC) inhibitors.
机构信息
Department of Medicinal Chemistry and Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 250012 Jinan, Shandong, PR China.
Department of Pharmaceutical Analysis and Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Cheeloo College of Medicine, Shandong University, 250012 Jinan, Shandong, PR China.
出版信息
Bioorg Med Chem. 2023 May 1;85:117242. doi: 10.1016/j.bmc.2023.117242. Epub 2023 Mar 18.
The inhibition of histone deacetylases (HDACs) has been considered a promising therapeutic strategy for treatment of many diseases, especially cancer. In the current study, a series of 8-substituted quinoline-2-carboxamide derivatives were designed and synthesized as potent HDAC inhibitors. The most potent compound 21 g (IC = 0.050 µM) exhibited 3-fold greater HDAC inhibitory activity compared to the known HDAC inhibitor Vorinostat (IC = 0.137 µM). Additionally, compound 21g exhibited low toxicity against normal cells(IC in HUVEC cell > 50 µM) and showed good liver microsomal stability, therefore, may serve as a new lead compound for further development.
组蛋白去乙酰化酶（HDACs）的抑制作用被认为是治疗多种疾病（尤其是癌症）的一种很有前途的治疗策略。在目前的研究中，设计并合成了一系列 8-取代喹啉-2-甲酰胺衍生物作为有效的 HDAC 抑制剂。最有效的化合物 21g（IC = 0.050µM）的 HDAC 抑制活性比已知的 HDAC 抑制剂伏立诺他（IC = 0.137µM）高 3 倍。此外，化合物 21g 对正常细胞（HUVEC 细胞中 IC > 50µM）的毒性较低，并且显示出良好的肝微粒体稳定性，因此，可能作为进一步开发的新先导化合物。
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