Inhibition of p53-Murine Double Minute 2 (MDM2) Interactions with 3,3′-Spirocyclopentene Oxindole Derivatives

3,3′-Spirocyclopentene oxindoles structurally related to Wang’s spiropyrrolidine oxindoles have been highlighted as a new class of antiproliferative agents against cancer cell lines with wild-type p53 status (IC50 up to 0.96 μM on SJSA-1 and 2.9 μM in HCT116 p53-wt). Inhibition of the MDM2-p53 inter...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2018-10, Vol.61 (20), p.9386-9392
Main Authors: Gicquel, Maxime, Gomez, Catherine, Garcia Alvarez, Maria Concepcion, Pamlard, Olivier, Guérineau, Vincent, Jacquet, Eric, Bignon, Jérôme, Voituriez, Arnaud, Marinetti, Angela
Format: Article
Language:English
Subjects:
Chemical Sciences
Life Sciences
Organic chemistry
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Summary:3,3′-Spirocyclopentene oxindoles structurally related to Wang’s spiropyrrolidine oxindoles have been highlighted as a new class of antiproliferative agents against cancer cell lines with wild-type p53 status (IC50 up to 0.96 μM on SJSA-1 and 2.9 μM in HCT116 p53-wt). Inhibition of the MDM2-p53 interactions has been demonstrated through in vitro HTRF assays (IC50 up to 3.1 nM), while Western blot analysis showed activation of p53 selectively in HCT116 cancer cell lines with wild-type p53.
ISSN:0022-2623
1520-4804
DOI:10.1021/acs.jmedchem.8b01137