Insights into the structure?activity relationship of a type III secretion system inhibitor, aurodox
Insights into the structure?activity relationship of a type III secretion system inhibitor, aurodox
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深入了解 III 型分泌系统抑制剂 aurodox 的构效关系
DOI：
10.1016/j.bmcl.2022.128779
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发表时间：
2022
期刊：
影响因子：
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通讯作者：
Asami Yukihiro
中科院分区：
文献类型：
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作者：
Kimishima Aoi;Hagimoto Daichi;Honsho Masako;Watanabe Yoshihiro;Iwatsuki Masato;Tsutsumi Hayama;Inahashi Yuki;Naher Kamrun;Sakai Kazunari;Kuwae Asaomi;Abe Akio;Asami Yukihiro
Aurodox最初于1972年作为线性聚酮化合物分离，其对革兰氏阳性菌表现出抗菌活性。我们已经确定了aurodox作为一个特定的抑制剂的细菌III型分泌系统（T3 SS）使用我们原来的筛选系统抑制T3 SS介导的溶血在肠致病性大肠杆菌（EPEC）。本研究合成了15个Aurodox衍生物，并对它们的EPEC T3 SS抑制活性和对EPEC的抗菌活性进行了评价。其中一种衍生物对T3 SS抑制具有高度选择性，相当于aurodox，但没有表现出抗菌活性（69倍选择性）。这项工作揭示了结构-活性关系的抑制T3 SS的aurodox，并表明，T3 SS的目标是不同的抗菌活性的目标。
Aurodox was originally isolated in 1972 as a linear polyketide compound exhibiting antibacterial activity against Gram-positive bacteria. We have since identified aurodox as a specific inhibitor of the bacterial type III secretion system (T3SS) using our original screening system for inhibition of T3SS-mediated hemolysis in enteropathogenicEscherichia coli(EPEC). In this research, we synthesized 15 derivatives of aurodox and evaluated EPEC T3SS inhibitory activity as well as antibacterial activity against EPEC. One of the derivatives was highly selective for T3SS inhibition, equivalent to that of aurodox, but without exhibiting antibacterial activity (69-fold selectivity). This work revealed the structure–activity relationship for the inhibition of T3SS by aurodox and suggests that the target of T3SS is distinct from the target for antibacterial activity.