Isolation and acetylcholinesterase inhibitory activity of asterric acid derivatives produced by Talaromyces aurantiacus FL15, an endophytic fungus from Huperzia serrata.

Alzheimer's disease (AD) is a neurodegenerative disease and the fourth leading cause of death after cardiovascular disease, tumors, and stroke. Acetylcholinesterase (AChE) inhibitors, which are based on cholinergic damage, remain the mainstream drugs to alleviate AD-related symptoms. This study aimed to explore novel AChE inhibitors produced by the endophytic fungus FL15 from Huperzia serrata. The fungus was identified as Talaromyces aurantiacus FL15 according to its morphological characteristics and ITS, 18S rDNA, and 28S rDNA sequence analysis. Subsequently, seven natural metabolites were isolated from strain FL15, and identified as asterric acid (1), methyl asterrate (2), ethyl asterrate (3), emodin (4), physcion (5), chrysophanol (6), and sulochrin (7). Compounds 1-3, which possess a diphenyl ether structure, exhibited highly selective and moderate AChE inhibitory activities with IC50 values of 66.7, 23.3, and 20.1 μM, respectively. The molecular docking analysis showed that compounds 1-3 interacted with the active catalytic site and peripheral anionic site of AChE, and the esterification substitution groups at position 8 of asterric acid may contribute to its bioactivity. The asterric acid derivatives showed highly selective and moderate AChE inhibitory activities, probably via interaction with the peripheral anionic site and catalytic site of AChE. To the best of our knowledge, this study was the first report of the AChE inhibitory activity of asterric acid derivatives, which opens new perspectives for the design of more effective derivatives that could serve as a drug carrier for new chemotherapeutic agents to treat AD. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-022-03125-2. © King Abdulaziz City for Science and Technology 2022.