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α-Mangostin and Gambogic Acid as Potential Inhibitors of the p53–MDM2 Interaction Revealed by a Yeast Approach

2013; American Chemical Society; Volume: 76; Issue: 4 Linguagem: Inglês

10.1021/np400049j

1520-6025

Miguel Leão, Sara Gomes, José Pedraza‐Chaverrí, Neuza Machado, Emı́lia Sousa, Madalena Pinto, Alberto Inga, Clara Pereira, Lucı́lia Saraiva,

Carbohydrate Chemistry and Synthesis

α-Mangostin (1) and gambogic acid (2) are natural products with potent cytotoxic activity against several human tumor cells. However, their molecular mechanisms of action remain controversial. In this work, using yeast-based assays, it was shown that both xanthones are potential inhibitors of the p53–MDM2 interaction. This activity on p53–MDM2 interaction was confirmed by a gene reporter assay in a human tumor cell. Additionally, computational docking studies supported the potential of these xanthones to bind to MDM2 and therefore act as putative MDM2 inhibitors. Altogether, this work provides a new insight concerning the molecular basis of activity for these compounds.