title: Α-mangostin and gambogic acid as potential inhibitors of the p53-MDM2 interaction revealed by a yeast approach.
abstract: 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.
authors.affiliation: REQUIMTE, Laboratório de Microbiologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal.
authors.forename: Mariana
authors.initials: M
authors.lastname: Leão
authors.forename: Sara
authors.initials: S
authors.lastname: Gomes
authors.forename: José
authors.initials: J
authors.lastname: Pedraza-Chaverri
authors.forename: Neuza
authors.initials: N
authors.lastname: Machado
authors.forename: Emília
authors.initials: E
authors.lastname: Sousa
authors.forename: Madalena
authors.initials: M
authors.lastname: Pinto
authors.forename: Alberto
authors.initials: A
authors.lastname: Inga
authors.forename: Clara
authors.initials: C
authors.lastname: Pereira
authors.forename: Lucília
authors.initials: L
authors.lastname: Saraiva
mesh_terms: D015153:Blotting, Western; D028084:Clusiaceae / Q000737:chemistry*; D005638:Fruit / Q000737:chemistry; D006801:Humans; D015394:Molecular Structure; D051736:Proto-Oncogene Proteins c-mdm2 / Q000037:antagonists & inhibitors*; D012116:Resins, Plant / Q000737:chemistry; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors*; D044004:Xanthones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D015003:Yeasts / Q000378:metabolism
chemical_list: D012116:Resins, Plant; D016159:Tumor Suppressor Protein p53; D044004:Xanthones; C052659:gambogic acid; D051736:Proto-Oncogene Proteins c-mdm2; C021053:mangostin