Discovery of Novel Isatin-Based p53 Inducers.
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.
St. Petersburg Technological Institute , 26, Moskovskii Av., St. Petersburg 190013, Russia.
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Davidovich
St. Petersburg Technological Institute , 26, Moskovskii Av., St. Petersburg 190013, Russia.
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Aksenova
St. Petersburg Technological Institute , 26, Moskovskii Av., St. Petersburg 190013, Russia ; MRC Toxicology Unit, University of Leicester , Lancaster Road, Leicester LE1 9HN, United Kingdom.
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Petrova
St. Petersburg Technological Institute , 26, Moskovskii Av., St. Petersburg 190013, Russia ; Institute of Cytology , 4, Tikhoretsky Av., St. Petersburg 194064, Russia.
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Tentler
St. Petersburg Technological Institute , 26, Moskovskii Av., St. Petersburg 190013, Russia.
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Orlova
St. Petersburg State University , Universitetsky Av. 26, St. Petersburg 198504, Russia.
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Smirnov
St. Petersburg State University , Universitetsky Av. 26, St. Petersburg 198504, Russia.
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Gurzhiy
Wolfson Institute for Biomedical Research, University College London , Gower Street, London WC1E 6BT, United Kingdom.
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Okorokov
St. Petersburg Technological Institute , 26, Moskovskii Av., St. Petersburg 190013, Russia.
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Garabadzhiu
St. Petersburg Technological Institute , 26, Moskovskii Av., St. Petersburg 190013, Russia ; MRC Toxicology Unit, University of Leicester , Lancaster Road, Leicester LE1 9HN, United Kingdom.
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Melino
St. Petersburg Technological Institute , 26, Moskovskii Av., St. Petersburg 190013, Russia ; Institute of Cytology , 4, Tikhoretsky Av., St. Petersburg 194064, Russia.
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Barlev
St. Petersburg Technological Institute , 26, Moskovskii Av., St. Petersburg 190013, Russia.
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Tribulovich
MDM2; in silico; in vivo assay; isatin Mannich and Schiff bases; p53 activators; protein−protein interactions