Bioactive Alkaloids With Anti-Neuroinflammatory Activity From Mangrove Sediment-Derived Fungus Pseudallescheria sp....

Chemical analysis of the fungus Pseudallescheria sp. SYSU-M4, isolated from mangrove sediments and grown on rice medium, yielded sixteen alkaloids (1-16), including two new compounds dihydroversimide B (1) and glulisine B (3), two new natural products 6S-dihydroversimide (2) and 2,3,6,7-tetrahydro-3-isobutylpyrrolo[1,2-a]pyrazine-1,4-dione (5), along with twelve known alkaloids. 1D and 2D NMR data analysis established their structures. The absolute configurations of Compounds 1 and 2 were assigned using an integrated approach involving electronic circular dichroism (ECD) and ¹³C NMR calculations, as well as DP4+ analysis. The anti-neuroinflammatory and acetylcholinesterase (AChE) inhibitory activities for selected isolated alkaloids were tested. Specifically, Compounds 1, 7, 10, and 11 dose-dependently suppressed lipopolysaccharide (LPS)-induced nitric oxide (NO) accumulation in BV-2 cells at 20.0 µg/mL and without cytotoxicity at this effective concentration. Notably, these compounds moderately attenuated LPS-stimulated BV-2 cell activation by downregulating interleukin-1β (IL-1β), indicating their potential anti-inflammatory effects. Additionally, Compound 11 exhibited slight to moderate AChE inhibitory activity, with an IC₅₀ of 82.2 µM.