Phenolic bisabolane and cuparene sesquiterpenoids with anti-inflammatory activities from the deep-sea-derived Aspergillus sydowii MCCC 3A00324 fungus
Phenolic bisabolane and cuparene sesquiterpenoids with anti-inflammatory activities from the deep-sea-derived Aspergillus sydowii MCCC 3A00324 fungus
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来自深海的 Aspergillus sydowii MCCC 3A00324 真菌，具有抗炎活性的酚红没药烷和铜烯倍半萜类化合物
DOI：
10.1016/j.bioorg.2020.104420
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发表时间：
2020-12-01
影响因子：
5.1
通讯作者：
Shao, Zongze
中科院分区：
文献类型：
--
作者：
Niu, Siwen;Yang, Longhe;Shao, Zongze
从深海底泥真菌AspergillusSydowii MCCC 3A00324发酵培养物的乙酸乙酯萃取物中分离得到17个未见文献报道的倍半萜类化合物，其中包括14个酚性双没食烷A-N(1-14)和3个铜烯(Aspperparenes A-C，15-17)，以及10个已知的双倍半萜类似物(18-27)。新结构是在广泛的核磁共振和HRESIMS光谱数据分析的基础上建立的，而其绝对构型是通过将实验ECD谱与TDDFT-ECD计算谱或文献报道的数据进行比较来指认的。曲霉烷A(1)和B(2)是以6/6/6三环核为特征的双二酚类倍半萜的第一个例子。化合物3具有一个新的二氧杂环己烷骨架，具有稀有的二氧杂环戊环部分，而天冬青K(11)代表了第一个含有稀有甲磺酰基的双杂环烷。对分离得到的化合物(1-27)在脂多糖激活的BV-2小胶质细胞中抑制NO分泌的活性进行了评价。结果表明，在10 mM浓度下，6、12、16和25-27的抑制率均在45%以上，且12通过抑制核因子-kappaB激活途径发挥抗炎作用，且呈剂量依赖关系。
Seventeen undescribed sesquiterpenoids including 14 phenolic bisabolanes, namely asperbisabolanes A-N (1-14), and 3 cuparenes (aspercuparenes A-C, 15-17), together with 10 known bisabolane analogues (18-27) were isolated from the EtOAc extract of fermented cultures of the deep sea sediment-derived fungus Aspergillus sydowii MCCC 3A00324. The new structures were established on the basis of extensive NMR and HRESIMS spectroscopic data analyses, while their absolute configurations were assigned by comparison of the experimental ECD spectra with those of the TDDFT-ECD calculated spectra or reported data in literature. Asperbisabolanes A (1) and B (2) are the first examples of bisabolane sesquiterpenoids featuring a 6/6/6 tricyclic nucleus. Compound 3 possessed a novel seco-bisabolane skeleton with a rare dioxolane ring moiety, while asperbisabolane K (11) represents the first case of bisabolanes bearing a rare methylsulfonyl group. All the isolated compounds (1-27) were evaluated their activities against NO secretion in LPS-activated BV-2 microglia cells. As a result, 6, 12, 16, and 25-27 exhibited the inhibition rate over 45% at a concentration of 10 mu M. Moreover, 12 exerted the anti-inflammatory activity by inhibiting the NF-kappa B-activated pathway in dose-dependent manner.