REQUIMTE, Laboratório de Microbiologia, Departamento de Ciências Biológicas, Faculdade de Farmácia, Universidade do Porto, 4050-313 Porto, Portugal.
J Nat Prod. 2013 Apr 26;76(4):774-8. doi: 10.1021/np400049j. Epub 2013 Mar 29.
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.
倒捻子素（1）和藤黄酸（2）是具有针对多种人类肿瘤细胞的强大细胞毒性活性的天然产物。然而，它们的作用机制仍存在争议。在这项工作中，使用酵母为基础的测定法，表明这两种二氢黄酮都可能抑制 p53-MDM2 相互作用。在人类肿瘤细胞中的基因报告检测中，证实了这种对 p53-MDM2 相互作用的活性。此外，计算对接研究支持这些二氢黄酮与 MDM2 结合的潜力，因此可以作为潜在的 MDM2 抑制剂。总之，这项工作为这些化合物的活性的分子基础提供了新的见解。
