Chemical and biological profiling of bioactive metabolites from the invertebrate-pathogenic fungus Gibellula scorpioides BCC 39989

Gibellula scorpioides BCC 39989 is one of the species of spider-parasitic Gibellula (Hypocreales, Cordycipitaceae) discovered in Thailand. Investigation of the invertebrate-pathogenic fungus G. scorpioides BCC 39989 led to the isolation of eight known compounds (1-8). Their chemical structures were determined by employing extensive spectroscopic analysis. Among them, ergosterol peroxide (1) and methyl o-hydroxycinnamate (2) exhibited significant biological activities. Both compounds notably suppressed LPS-induced nitric oxide production and reduced IL-6 and TNF-α secretion in RAW264.7 macrophages. In addition, compounds 1, 2, and oleic acid (7) significantly inhibited lipid accumulation and reduced intracellular triglyceride content in 3T3-L1 adipocytes in a dose-dependent manner. Compound 1 also displayed potent antiproliferative activity against human colorectal adenocarcinoma (SW480) cells, with an IC₅₀ value of 13.33 µg/mL, whereas compound 2 was less effective. Genotoxicity evaluation of ergosterol peroxide (1) using the cytokinesis-block micronucleus assay in V79 cells revealed no genotoxic effects at concentrations ranging from 3.125 to 50 µg/mL, both with and without metabolic activation. These findings highlight G. scorpioides as a promising source of bioactive compounds, particularly ergosterol peroxide (1), which exhibits potent anti-inflammatory, anti-adipogenic, and antiproliferative properties without genotoxicity.