AUTHOR=Amaral Joana D. , Silva Dário , Rodrigues Cecília M. P. , Solá Susana , Santos Maria M. M. TITLE=A Novel Small Molecule p53 Stabilizer for Brain Cell Differentiation JOURNAL=Frontiers in Chemistry VOLUME=7 YEAR=2019 URL=https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2019.00015 DOI=10.3389/fchem.2019.00015 ISSN=2296-2646 ABSTRACT=
Brain tumor, as any type of cancer, is assumed to be sustained by a small subpopulation of stem-like cells with distinctive properties that allow them to survive conventional therapies and drive tumor recurrence. Thus, the identification of new molecules capable of controlling stemness properties may be key in developing effective therapeutic strategies for cancer by inducing stem-like cells differentiation. Spiropyrazoline oxindoles have previously been shown to induce apoptosis and cell cycle arrest, as well as upregulate p53 steady-state levels, while decreasing its main inhibitor MDM2 in the HCT116 human colorectal carcinoma cell line. In this study, we made modifications in this scaffold by including combinations of different substituents in the pyrazoline ring in order to obtain novel small molecules that could modulate p53 activity and act as differentiation inducer agents. The antiproliferative activity of the synthesized compounds was assessed using the isogenic pair of HCT116 cell lines differing in the presence or absence of the p53 gene. Among the tested spirooxindoles, spiropyrazoline oxindole