Design, synthesis and biological evaluation of sulfamide and triazole benzodiazepines as novel p53-MDM2 inhibitors.
Design, synthesis and biological evaluation of sulfamide and triazole benzodiazepines as novel p53-MDM2 inhibitors.
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作为新型 p53-MDM2 抑制剂的磺酰胺和三唑苯二氮卓类药物的设计、合成和生物学评价
DOI：
10.3390/ijms150915741
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发表时间：
2014-09-05
影响因子：
5.6
通讯作者：
Zhang W
中科院分区：
文献类型：
--
作者：
Yu Z;Zhuang C;Wu Y;Guo Z;Li J;Dong G;Yao J;Sheng C;Miao Z;Zhang W
利用生物电子等排原理得到了一系列磺酰胺和三唑苯二氮卓类药物。评估了p53-鼠双分钟2（MDM2）抑制活性和体外抗肿瘤活性。大多数新型苯二氮卓类药物表现出中等的蛋白质结合抑制活性。特别是，三唑苯二氮卓类药物显示出良好的抑制活性和抗肿瘤效力。化合物16对U-2 OS人骨肉瘤细胞系具有良好的抗肿瘤活性，IC50值为4.17 μM，明显优于nutlin-3。分子对接模型还成功预测此类化合物模仿了p53与MDM2结合的三个关键残基。
A series of sulfamide and triazole benzodiazepines were obtained with the principle of bioisosterism. The p53-murine double minute 2 (MDM2) inhibitory activity and in vitro antitumor activity were evaluated. Most of the novel benzodiazepines exhibited moderate protein binding inhibitory activity. Particularly, triazole benzodiazepines showed good inhibitory activity and antitumor potency. Compound 16 had promising antitumor activity against the U-2 OS human osteosarcoma cell line with an IC50 value of 4.17 μM, which was much better than that of nutlin-3. The molecular docking model also successfully predicted that this class of compounds mimicked the three critical residues of p53 binding to MDM2.
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影响因子：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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通讯作者：
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