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Synthesis and Biological Evaluation of Novel Dispiro Compounds based on 5-Arylidenehydantoins and Isatins as Inhibitors of p53–MDM2 Protein–Protein Interaction
Chemistry of Heterocyclic Compounds ( IF 1.4 ) Pub Date : 2020-07-23 , DOI: 10.1007/s10593-020-02726-0
Anastasia Beloglazkina , Alexander Barashkin , Vladislav Polyakov , German Kotovsky , Nikita Karpov , Sofia Mefedova , Bogdan Zagribelny , Yan Ivanenkov , Marina Kalinina , Dmitry Skvortsov , Victor Tafeenko , Nikolay Zyk , Alexander Majouga , Elena Beloglazkina

A series of novel hydantoin-based dispiroindolinones as potential small-molecule inhibitors of p53–MDM2 protein–protein interaction were synthesized by two methods, using 2-arylidenehydantoins as starting materials. Some compounds demonstrate moderate cytotoxicity against cancer cell lines with IC50 in micromolar concentration range, which is comparable to nutlin-3. Two of the synthesized dispiroindolinones show p53-related activity in p53 reporter activation test.


中文翻译:

基于5-丙烯醛乙内酰脲和Isatins作为p53–MDM2蛋白与蛋白质相互作用抑制剂的新型Dispiro化合物的合成和生物学评估

以2-芳基乙内酰脲为起始原料,通过两种方法合成了一系列基于乙内酰脲的新型双螺吲哚酮类化合物作为潜在的小分子p53–MDM2蛋白-蛋白相互作用抑制剂。一些化合物在微摩尔浓度范围内对IC50表现出对癌细胞系的中等细胞毒性,这与nutlin-3相当。两种合成的双螺吲哚满酮在p53报告基因激活试验中显示p53相关活性。
更新日期:2020-07-23
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