Anti-Aβ42 Aggregative Polyketides from the Antarctic Psychrophilic Fungus Pseudogymnoascus sp. OUCMDZ-3578
Anti-Aβ42 Aggregative Polyketides from the Antarctic Psychrophilic Fungus Pseudogymnoascus sp. OUCMDZ-3578
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DOI：
10.1021/acs.jnatprod.2c01101
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发表时间：
2023-03-02
影响因子：
5.1
通讯作者：
Wang, Yi
中科院分区：
文献类型：
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作者：
Han, Xiaoling;Gao, Hai;Wang, Yi
从嗜冷真菌Pseudogymnococcus sp. OUCMDZ-3578中分离得到7个新的聚酮化合物，即二苯酮（1）、二苯酮糖苷（2-4）、二苯酮-二苯醚二聚体（6）、蒽醌-二苯酮二聚体（7和8）以及化合物5。通过酸水解和1-苯基-3-甲基-5-吡唑啉酮柱前衍生化确定了2-4的绝对构型。通过X射线衍射分析首次确定了5的构型。化合物6和8显示出对淀粉样蛋白β（AP 42）聚集的最高活性，半最大抑制浓度（IC 50）分别为0.10和0.18 μ M。它们对金属离子，特别是铁离子具有很强的螯合能力，对金属离子诱导的AP 42聚集敏感，并具有解聚活性。化合物6和8显示出作为用于治疗阿尔茨海默病以防止AP 42聚集的先导物的潜力。
Seven new polyketides, diphenyl ketone (1), diphenyl ketone glycosides (2-4), diphenyl ketone-diphenyl ether dimer (6), and anthraquinone-diphenyl ketone dimers (7 and 8), together with compound 5, were isolated from the psychrophilic fungus Pseudogymnoascus sp. OUCMDZ-3578 fermented at 16 degrees C and identified by spectroscopic analysis. The absolute configurations of 2-4 were determined by acid hydrolysis and 1-phenyl-3-methyl-5-pyrazolone precolumn derivatization. The configuration of 5 was first determined by X-ray diffraction analysis. Compounds 6 and 8 showed the highest activity against amyloid beta (AP42) aggregation with half-maximal inhibitory concentrations (IC50) of 0.10 and 0.18 mu M, respectively. They also showed strong abilities to chelate with metal ions, especially iron, were sensitive to AP42 aggregation induced by metal ions, and displayed depolymerizing activity. Compounds 6 and 8 show potential as leads for the treatment of Alzheimer's disease to prevent AP42 aggregation.