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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

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
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Abstract


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.


Keywords


hydantoins; spirooxindole; anticancer drugs; 1,3-dipolar cycloaddition; p53–MDM2 inhibitors.

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