1,4-二烯-3-酮苯甲酰胺类化合物的设计、合成及抗肿瘤活性研究

Design,synthesis and pharmacological activities of 1,4-dien-3-one benzamides derivatives

目的设计合成一系列1,4-二烯-3-酮苯甲酰胺类(组蛋白去乙酰化酶HDACs)抑制剂,并评价其对A549、Hep3B、PANC-1肿瘤细胞的体外抗增殖活性,为后续设计合成高活性化合物提供参考。方法以临床在研药物MS-275为基础,通过生物电子等排原理设计具有新型骨架结构的HDAC抑制剂,采用MTS法测定化合物对肿瘤细胞的体外抗增殖活性。结果与结论合成了8个未见文献报道的新型HDACs抑制剂,目标化合物结构均经MS、~1H-NMR谱确证。肿瘤细胞实验表明,所有化合物对A549、Hep3B、PANC-1细胞均具有较强的抗增殖活性,具有深入研究的价值。

Histone deacelases （HDACs） play an important role in the promotion of malignant tumor cell development, survival and metastasis. HDACs have been identified as one of the most attractive target for new anticancer drug development. Based on the analysis of SAR of HDACs inhibitors, eight 1,4-dien-3-one benzamides HDACs kinase inhibitors were designed and synthesized. The target compounds were prepared through different methods with mild conditions and high yields. The structures of the target compounds were identified by MS and ^1H-NMR spectra. The results of biological evaluation indicated that all compounds showed high potency activities against A549, Hep3B, PANC-1 cancer cells, and further evaluation of these compounds are currently under investigation.