Synthesis and Biological Evaluation of Novel Dispiro Compounds based on 5-Arylidenehydantoins and Isatins as Inhibitors of p53-MDM2 Protein-Protein Interaction

被引：16

作者：

Beloglazkina, Anastasia ^{[1
]}

Barashkin, Alexander ^{[1
]}

Polyakov, Vladislav ^{[1
]}

Kotovsky, German ^{[1
]}

Karpov, Nikita ^{[1
]}

Mefedova, Sofia ^{[1
]}

Zagribelny, Bogdan ^{[1
,2
]}

Ivanenkov, Yan ^{[2
]}

Kalinina, Marina ^{[3
]}

Skvortsov, Dmitry ^{[1
,4
]}

Tafeenko, Victor ^{[1
]}

Zyk, Nikolay ^{[1
]}

Majouga, Alexander ^{[1
,5
,6
]}

Beloglazkina, Elena ^{[1
]}

机构：

[1] Lomonosov Moscow State Univ, 1 Build 3 Leninskie Gory, Moscow 119991, Russia

[2] Moscow Inst Phys & Technol, 9 Inst Skiy Pereulok, Dolgoprudnyi 141700, Moscow Region, Russia

[3] Skolkovo Inst Sci & Technol, 4 Alfred Nobel St, Skolkovo 143025, Russia

[4] Higher Sch Econ, Fac Biol & Biotechnol, 7 Vavilova St, Moscow 117312, Russia

[5] Natl Univ Sci & Technol MISiS, 9 Leninsky Ave, Moscow 119049, Russia

[6] D Mendeleev Univ Chem Technol Russia, 9 Miusskaya Sq, Moscow 125047, Russia

来源：

CHEMISTRY OF HETEROCYCLIC COMPOUNDS | 2020年 / 56卷 / 06期

基金：

俄罗斯科学基金会;

关键词：

hydantoins; spirooxindole; anticancer drugs; 1,3-dipolar cycloaddition; p53-MDM2; inhibitors; SMALL-MOLECULE; P53; PATHWAY; CANCER; DERIVATIVES; MDM2; CYCLOADDITION; ACTIVATION; DISCOVERY; POTENT;

D O I：

10.1007/s10593-020-02726-0

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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.

引用

页码：747 / 755

页数：9

共 31 条

[1] The structure of an MDM2-Nutlin-3a complex solved by the use of a validated MDM2 surface-entropy reduction mutant [J].