Acetylcholinesterase inhibitors and antioxidants mining from marine fungi: bioassays, bioactivity coupled LC-MS/MS analyses and molecular networking
Acetylcholinesterase inhibitors and antioxidants mining from marine fungi: bioassays, bioactivity coupled LC-MS/MS analyses and molecular networking
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从海洋真菌中提取乙酰胆碱酯酶抑制剂和抗氧化剂：生物测定、生物活性耦合 LC–MS/MS 分析和分子网络
DOI：
10.1007/s42995-020-00065-9
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发表时间：
2020-11-01
影响因子：
5.7
通讯作者：
Zhang, Yi
中科院分区：
文献类型：
--
作者：
Nie, Yingying;Yang, Wencong;Zhang, Yi
海洋真菌是潜在的重要生物活性先导化合物资源，可用于发现治疗阿尔茨海默病等疾病的新药。采用乙酰胆碱酯酶（AChE）抑制、DPPH自由基清除和卤虫幼虫致死率的联合生物测定模型，对35株海洋真菌菌株的活性和毒性进行了评价。通过薄层色谱（TLC）、生物活性联用LC-MS/MS和全球天然产物社会分子网络（GNPS）等方法对它们的活性成分进行了研究。结果表明，5株菌的提取物对乙酰胆碱酯酶的抑制率均高于阳性对照化合物“他克林”，后者在200 μ g/ml时的抑制率为89.8%。6株菌株对AChE的抑制率> 20%，对DPPH的清除率> 30%，对卤虫幼虫的致死率< 12%。薄层层析结果表明，四株菌的分离提取物中含有丰富的活性成分，包括Talaromyces sp. C21-1、Aspergillus terreus C23-3、Trichoderma harzianum DLEN 2008005和Penicillium corylophilum TBG 1 -17。从最有效的样品F-11-1-B（来源于土曲霉C23-3）中，通过AChE耦合超滤随后LC-MS/MS和LC-MS/MS耦合DPPH孵育识别出5种AChE抑制剂和7种抗氧化剂为生物活性分子。在GNPS的帮助下，AChE抑制剂被合理地注释为土曲林类似物，包括土曲林A-C/D、阿里舒加星A和未知化合物4，而7种抗氧化剂被指定为丁内酯。曲霉素E，一种酚类衍生物和可能未知的化合物8-10和12。
Marine fungi are potentially important resources for bioactive lead compounds for discovering new drugs for diseases such as Alzheimer's disease. In this paper, the combined bioassay model of acetylcholinesterase (AChE) inhibition, 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical scavenging, and Artemia larval lethality was used to evaluate the activity and toxicity of 35 marine fungal strains from seas around China. Their bioactive constituents were revealed by thin layer chromatography (TLC) autography, bioactivity coupled LC-MS/MS and Global Natural Products Social Molecular Networking (GNPS). The results show that the extracts of five strains exhibited higher AChE inhibition ratios than the positive control compound, 'tacrine', for which the ratio was 89.8% at 200 mu g/ml. Six strains displayed both AChE inhibition (inhibition ratios > 20% at 200 mu g/ml) and DPPH scavenging activity (scavenging ratios > 30% at 200 mu g/ml) together with low Artemia larval toxicity (lethal rates < 12%). TLC autography showed that the fractioned extracts of four strains contained highly diverse and different bioactive constituents, including strains Talaromyces sp. C21-1, Aspergillus terreus C23-3, Trichoderma harzianum DLEN2008005, and Penicillium corylophilum TBG1-17. From the most potent sample F-11-1-b (derived from Aspergillus terreus C23-3), five AChE inhibitors and seven antioxidants were recognized as bioactive molecules by AChE coupled ultrafiltration followed by LC-MS/MS, and LC-MS/MS coupled with DPPH incubation. Furthermore, with the aid of GNPS, the AChE inhibitors were plausibly annotated as territrem analogues including territrems A-C/D, arisugacin A and an unknown compound 4, and the seven antioxidants were assigned as butyrolactone., aspernolide E, a phenolic derivative and possibly unknown compounds 8-10 and 12.