来源于佛司可林 A 的短梗霉烯 A 类似物的半合成及生物评价。
Semisynthesis and biological evaluation of a cotylenin A mimic derived from fusicoccin A.
机构信息
The Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan.
The Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan.
出版信息
Bioorg Med Chem Lett. 2018 Feb 15;28(4):646-650. doi: 10.1016/j.bmcl.2018.01.030.
In an effort to overcome the unavailability of cotylenin A (CN A), an anticancer agent and a stabilizer of protein-protein interactions (PPIs) mediated by 14-3-3 proteins, ISIR-050 was designed as a CN A mimic. The synthesis was accomplished via a semisynthetic approach starting from fusicoccin A. ISIR-050 showed interferon-α (IFNα)-dependent growth inhibitory activity and a PPI stabilization effect similar to those of CN A. The biochemical analysis suggested that ISIR-050 and CN A induce the same pharmacological response to IFNα-treated cancer cells and that 14-3-3 proteins play a role in the mode of action.
为了克服抗癌药物和 14-3-3 蛋白介导的蛋白质-蛋白质相互作用（PPIs）稳定剂 cotylenin A（CN A）的不可用性，设计了 ISIR-050 作为 CN A 的模拟物。该合成通过从 fusicoccin A 开始的半合成方法完成。ISIR-050 表现出与 CN A 相似的干扰素-α（IFNα）依赖性生长抑制活性和 PPI 稳定作用。生化分析表明，ISIR-050 和 CN A 诱导 IFNα 处理的癌细胞产生相同的药理反应，并且 14-3-3 蛋白在作用模式中起作用。
Zotero 插件