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 language | English |
|---|---|
| Pages (from-to) | 856-860 |
| Number of pages | 5 |
| Journal | ACS Medicinal Chemistry Letters |
| Volume | 6 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 13 2015 |
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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
Cite this
Discovery of Novel Isatin-Based p53 Inducers. / Davidovich, P.; Aksenova, V.; Petrova, V.; Tentler, D.; Orlova, D.; Smirnov, S.; Gurzhiy, V.; Okorokov, A. L.; Garabadzhiu, A.; Melino, G.; Barlev, N.; Tribulovich, V.
In: ACS Medicinal Chemistry Letters, Vol. 6, No. 8, 13.08.2015, p. 856-860.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Discovery of Novel Isatin-Based p53 Inducers
AU - Davidovich, P.
AU - Aksenova, V.
AU - Petrova, V.
AU - Tentler, D.
AU - Orlova, D.
AU - Smirnov, S.
AU - Gurzhiy, V.
AU - Okorokov, A. L.
AU - Garabadzhiu, A.
AU - Melino, G.
AU - Barlev, N.
AU - Tribulovich, V.
PY - 2015/8/13
Y1 - 2015/8/13
N2 - 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.
AB - 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.
KW - in silico
KW - in vivo assay
KW - isatin Mannich and Schiff bases
KW - MDM2
KW - p53 activators
KW - protein-protein interactions
UR - http://www.scopus.com/inward/record.url?scp=84938917201&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84938917201&partnerID=8YFLogxK
U2 - 10.1021/acsmedchemlett.5b00011
DO - 10.1021/acsmedchemlett.5b00011
M3 - Article
VL - 6
SP - 856
EP - 860
JO - ACS Medicinal Chemistry Letters
JF - ACS Medicinal Chemistry Letters
SN - 1948-5875
IS - 8
ER -