Semisynthesis and biological evaluation of a cotylenin A mimic derived from fusicoccin A
Semisynthesis and biological evaluation of a cotylenin A mimic derived from fusicoccin A
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DOI：
10.1016/j.bmcl.2018.01.030
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发表时间：
2018-02-15
影响因子：
2.7
通讯作者：
Kato, Nobuo
中科院分区：
文献类型：
--
作者：
Inoue, Takatsugu;Higuchi, Yusuke;Kato, Nobuo
为了克服子叶蛋白 A (CNA) 的不可用性，子叶蛋白 A (CNA) 是一种抗癌剂和由 14-3-3 蛋白介导的蛋白质-蛋白质相互作用 (PPI) 的稳定剂，ISIR-050 被设计为 CNA 模拟物。该合成是通过半合成方法从 Fusicoccin A 开始完成的。ISIR-050 显示出干扰素-α (IFN α) 依赖性生长抑制活性和与 CN A 相似的 PPI 稳定作用。生化分析表明，ISIR-050 和 CN A 对 IFNa 处理的癌细胞诱导相同的药理反应，并且 14-3-3 蛋白在作用模式中发挥作用。 (C) 2018 Elsevier Ltd. 保留所有权利。
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-alpha (IFN alpha)-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 IFNa-treated cancer cells and that 14-3-3 proteins play a role in the mode of action. (C) 2018 Elsevier Ltd. All rights reserved.