College of Medical and Life Sciences, Silla University, San 1-1 Gwaebeop-dong, Sasang-gu, Busan 617-736, Republic of Korea.
Bioorg Med Chem Lett. 2009 Nov 1;19(21):6095-7. doi: 10.1016/j.bmcl.2009.09.025. Epub 2009 Sep 12.
In the course of bioassay-guided study on the EtOAc extract of a culture broth of the marine-derived fungus Cosmospora sp. SF-5060, aquastatin A (1) was isolated as a protein tyrosine phosphatase 1B (PTP1B) inhibitory component produced by the fungus. The compound was isolated by various chromatographic methods, and the structure was determined mainly by analysis of NMR spectroscopic data. Compound 1 exhibited potent inhibitory activity against PTP1B with IC(50) value of 0.19muM, and the kinetic analyses of PTP1B inhibition by compound 1 suggested that the compound is inhibiting PTP1B activity in a competitive manner. Aquastatin A (1) also showed modest but selective inhibitory activity toward PTP1B over other protein tyrosine phosphatases, such as TCPTP, SHP-2, LAR, and CD45. In addition, the result of hydrolyzing aquastatin A (1) suggested that the dihydroxypentadecyl benzoic acid moiety in the molecule is responsible for the inhibitory activity.
在对海洋来源真菌 Cosmospora sp. SF-5060 的发酵液的 EtOAc 提取物进行基于生物测定的研究过程中，分离得到了化合物 1，其为该真菌产生的蛋白酪氨酸磷酸酶 1B（PTP1B）抑制剂成分。该化合物通过各种色谱方法分离得到，其结构主要通过 NMR 波谱数据分析确定。化合物 1 对 PTP1B 表现出很强的抑制活性，IC50 值为 0.19μM，化合物 1 对 PTP1B 抑制的动力学分析表明，该化合物以竞争性方式抑制 PTP1B 的活性。化合物 1 对 PTP1B 还表现出适度但选择性的抑制活性，而对其他蛋白酪氨酸磷酸酶如 TCPTP、SHP-2、LAR 和 CD45 的抑制活性则较弱。此外，化合物 1 的水解结果表明，分子中的二羟基十五烷基苯甲酸部分负责其抑制活性。
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