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- W3046868093 abstract "Abstract To search for novel p53 activators, four series of novel ( S )‐ and ( R )‐tryptophanol‐derived oxazoloisoindolinones were synthesized in a straightforward manner and their antiproliferative activity was evaluated in the human colorectal cancer HCT116 cell line. Structural optimization of the hit compound SLMP53‐1 led to the identification of a ( R )‐tryptophanol‐derived isoindolinone that was found to be six‐fold more active, with increased selectivity for HCT116 cells with p53 and with low toxicity in normal cells. Binding studies with MDM2 showed that the antiproliferative activity of tryptophanol‐derived isoindolinones does not involve inhibition of the main negative regulator of the p53 protein. Molecular docking simulations showed that although these molecules establish hydrophobic interactions with MDM2, they do not possess the required features to bind MDM2." @default.
- W3046868093 created "2020-08-07" @default.
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- W3046868093 date "2020-09-02" @default.
- W3046868093 modified "2023-10-18" @default.
- W3046868093 title "Potency and Selectivity Optimization of Tryptophanol‐Derived Oxazoloisoindolinones: Novel p53 Activators in Human Colorectal Cancer" @default.
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- W3046868093 doi "https://doi.org/10.1002/cmdc.202000522" @default.
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