Discovery of Novel Isatin-Based p53 Inducers

P. Davidovich, V. Aksenova, V. Petrova, D. Tentler, D. Orlova, S. Smirnov, V. Gurzhiy, A. L. Okorokov, A. Garabadzhiu, G. Melino, N. Barlev, V. Tribulovich

Research output: Contribution to journalArticlepeer-review

Abstract

A series of isatin Schiff base derivatives were identified during in silico screening of the small molecule library for novel activators of p53. The compounds selected based on molecular docking results were further validated by a high-content screening assay using U2OS human osteosarcoma cells with an integrated EGFP-expressing p53-dependent reporter. The hit compounds activated and stabilized p53, as shown by Western blotting, at higher rates than the well-known positive control Nutlin-3. Thus, the p53-activating compounds identified by this approach represent useful molecular probes for various cancer studies.

Original languageEnglish
Pages (from-to)856-860
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume6
Issue number8
DOIs
Publication statusPublished - Aug 13 2015

Keywords

  • in silico
  • in vivo assay
  • isatin Mannich and Schiff bases
  • MDM2
  • p53 activators
  • protein-protein interactions

ASJC Scopus subject areas

  • Organic Chemistry
  • Drug Discovery
  • Biochemistry

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