Sadahiro Yusaku, Hitora Yuki, Tsukamoto Sachiko
Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
J Nat Prod. 2021 Dec 24;84(12):3131-3137. doi: 10.1021/acs.jnatprod.1c00913. Epub 2021 Dec 2.
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 [Saos-2 (p53) cells] to search for compounds from natural sources that can target mut p53 and found an extract of sp. (13S020) that was active. Bioassay-guided fractionation of the extract afforded a known polyketide, colletofragarone A2 (), and three new analogues, colletoins A-C (-). The relative and absolute configurations of were determined by the spectroscopic method and DFT calculation. Compounds and inhibited the growth of Saos-2 (p53) cells and decreased mut p53 in the cells.
p53在肿瘤细胞中经常发生突变。突变型p53（mut p53）在细胞中积累，促进癌症进展、侵袭和转移，作为癌症治疗的靶点正受到关注。在本研究中，我们使用对多西环素诱导型p53的Saos-2细胞[Saos-2（p53）细胞]进行免疫荧光染色，从天然来源中寻找可靶向mut p53的化合物，并发现一种 sp.（13S020）的提取物具有活性。对该提取物进行生物测定导向的分级分离，得到一种已知的聚酮化合物，collectofragarone A2（），以及三个新类似物，collectoins A-C（-）。通过光谱方法和密度泛函理论计算确定了 的相对和绝对构型。化合物 和 抑制了Saos-2（p53）细胞的生长，并降低了细胞中的mut p53。
