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

doi:10.1021/np400049j

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 (Lead / Corresponding author)

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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.

Original language	English
Pages (from-to)	774-778
Number of pages	5
Journal	Journal of Natural Products
Volume	76
Issue number	4
DOIs	https://doi.org/10.1021/np400049j
Publication status	Published - 29 Mar 2013

ASJC Scopus subject areas

Analytical Chemistry
Molecular Medicine
Pharmacology
Pharmaceutical Science
Drug Discovery
Complementary and alternative medicine
Organic Chemistry

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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.",

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T1 - α-mangostin and gambogic acid as potential inhibitors of the p53-MDM2 interaction revealed by a yeast approach

AU - Leão, Mariana

AU - Gomes, Sara

AU - Pedraza-Chaverri, José

AU - MacHado, Neuza

AU - Sousa, Emília

AU - Pinto, Madalena

AU - Inga, Alberto

AU - Pereira, Clara

AU - Saraiva, Lucília

PY - 2013/3/29

Y1 - 2013/3/29

N2 - 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.

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

Abstract

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