Colletofragarone A2 and Colletoins A-C from a Fungus Colletotrichum sp. Decrease Mutant p53 Levels in Cells

被引：9

作者：

Sadahiro, Yusaku ^{[1
]}

Hitora, Yuki ^{[1
]}

Tsukamoto, Sachiko ^{[1
]}

机构：

[1] Kumamoto Univ, Grad Sch Pharmaceut Sci, Kumamoto 8620973, Japan

来源：

JOURNAL OF NATURAL PRODUCTS | 2021年 / 84卷 / 12期

关键词：

STABILIZATION; REACTIVATION; DEGRADATION; INHIBITION; PROTEASOME; MUTATIONS;

D O I：

10.1021/acs.jnatprod.1c00913

中图分类号：

Q94 [植物学];

学科分类号：

071001 ;

摘要：

p53 is frequently mutated in tumor cells. Mutant p53 (mut p53) accumulates in cells to promote cancer progression, invasion, and metastasis, and it is attracting attention as a target for cancer therapies. In this study, we used immunofluorescence staining of Saos-2 cells harboring doxycycline-inducible p53(R175H) [Saos-2 (p53(R175H)) cells] to search for compounds from natural sources that can target mut p53 and found an extract of Colletotrichum sp. (13S020) that was active. Bioassay-guided fractionation of the extract afforded a known polyketide, colletofragarone A2 (1), and three new analogues, colletoins A-C (2-4). The relative and absolute configurations of 1 were determined by the spectroscopic method and DFT calculation. Compounds 1 and 2 inhibited the growth of Saos-2 (p53(R175H)) cells and decreased mut p53 in the cells.

引用

页码：3131 / 3137

页数：7

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