Zhang_2025_Fitoterapia__106926

Chemical investigation on the EtOAc extract of endophytic fungus Talaromyces aculeatus A884 led to the isolation of one undescribed gamma-butyrolactone aculeatone A (1), one rubralactone aculeatone B (2), and one polyester aculeatone C (5) together with 12 known compounds. Their structures were unambiguously elucidated by extensive spectral analyses. The absolute configurations of aculeatones A-B were assigned by the comparison of their experimental and calculated ECD data. In addition, all of the isolates (1-15) were evaluated for their anti-inflammatory activities by measuring the inhibition of LPS-induced NO production in RAW 264.7 macrophages. Compounds 2, 9-11 exhibited significant anti-inflammatory activity with IC(50) values ranging from 24.17 to 29.56 microM, comparable with the positive control indomethacin (IC(50) = 29.44 microM). Further biological assessment showed that compound 2 displayed acetylcholinesterase (AChE) inhibitory activity with an IC(50) of 18.43 microM. Molecular docking simulations provided preliminary insights into the binding interactions between the new compound 2 and target proteins (iNOS and AChE).