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Journal of Natural Products 2013-04-26

Α-mangostin and gambogic acid as potential inhibitors of the p53-MDM2 interaction revealed by a yeast approach.

Mariana Leão, Sara Gomes, José Pedraza-Chaverri, Neuza Machado, Emília Sousa, Madalena Pinto, Alberto Inga, Clara Pereira, Lucília Saraiva

文献索引:J. Nat. Prod. 76(4) , 774-8, (2013)

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摘要

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.

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