Abstract
The secondary metabolites of Phaeosphaeria sp. LF5, an endophytic fungus with acetylcholinesterase (AChE) inhibitory activity isolated from Huperzia serrata, were investigated. Their structures and absolute configurations were elucidated by means of extensive spectroscopic data, including one- and two-dimensional nuclear magnetic resonance (NMR), high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) analyses, and calculations of electronic circular dichroism (ECD). A chemical study on the solid-cultured fungus LF5 resulted in 11 polyketide derivatives, which included three previously undescribed derivatives: aspilactonol I (4), 2-(1-hydroxyethyl)-6-methylisonicotinic acid (7), and 6,8-dihydroxy-3-(1′R, 2′R-dihydroxypropyl)-isocoumarin (9), and two new natural-source-derived aspilactonols (G, H) (2, 3). Moreover, the absolute configuration of de-O-methyldiaporthin (11) was identified for the first time. Compounds 4 and 11 exhibited inhibitory activity against AChE with half maximal inhibitory concentration (IC50) values of 6.26 and 21.18 µM, respectively. Aspilactonol I (4) is the first reported furanone AChE inhibitor (AChEI). The results indicated that Phaeosphaeria is a good source of polyketide derivatives. This study identified intriguing lead compounds for further research and development of new AChEIs.
Highlights
Introduction published maps and institutional affilNatural products are important sources of active compounds and play important roles in modern drug research and development
High-resolution electrospray ionization mass spectrometry (HR-ESI-MS) data were measured on a Waters ACQUITY UPLC H-Class
Semipreparative High-performance liquid chromatography (HPLC) was performed on a Waters 2535 Quaternary gradient module with a FlexInject, 2489 UV–VIS detector and Fraction Collector III (Waters, Milford, MA, USA)
Summary
Natural products are important sources of active compounds and play important roles in modern drug research and development. Endophytic fungi reside in the internal tissues of living plants without causing apparent disease. Due to their unique ecological niche, endophytic fungi have become important sources of natural products to be screened for with unique chemical structures and biological activity [3,4]. The natural product screening of endophytic fungi is currently a hot research topic [5–9]. In this sense, it is worth undertaking a constant search for novel compounds from endophytic fungal sources and paying attention to discovering potential drug candidates
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