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ACS Med Chem Lett. 2015 Jul 6;6(8):856-60. doi: 10.1021/acsmedchemlett.5b00011. eCollection 2015 Aug 13.

Discovery of Novel Isatin-Based p53 Inducers.

Author information

1
St. Petersburg Technological Institute , 26, Moskovskii Av., St. Petersburg 190013, Russia.
2
St. Petersburg Technological Institute , 26, Moskovskii Av., St. Petersburg 190013, Russia ; MRC Toxicology Unit, University of Leicester , Lancaster Road, Leicester LE1 9HN, United Kingdom.
3
St. Petersburg Technological Institute , 26, Moskovskii Av., St. Petersburg 190013, Russia ; Institute of Cytology , 4, Tikhoretsky Av., St. Petersburg 194064, Russia.
4
St. Petersburg State University , Universitetsky Av. 26, St. Petersburg 198504, Russia.
5
Wolfson Institute for Biomedical Research, University College London , Gower Street, London WC1E 6BT, United Kingdom.

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.

KEYWORDS:

MDM2; in silico; in vivo assay; isatin Mannich and Schiff bases; p53 activators; protein−protein interactions

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