Discovery of novel cytochalasin derivatives from an endophytic fungus isolated from Senecio doronicum

Plant fungal pathogens such as Botrytis cinerea pose a significant threat to global agriculture and forestry, causing crop yield losses, quality degradation, and even jeopardizing food security. It is estimated that fungal diseases account for annual crop losses of approximately 10% to 28% [ 1 ] [ 2 ]. Moreover, with the exacerbation of climate change, the spread and severity of fungal diseases are further increasing [ 3 ] [ 4 ]. Therefore, the search for novel antifungal agents to combat these phytopathogens is of great importance. In a screening campaign for the discovery of antifungal substances from endophytic microorganisms of alpine plants against B. cinerea , we have identified an endophytic fungus ( Ascomycota phylum) from the leaves of Senecio doronicum , displaying a promising bioactivity (MIC=25 μg/mL). The fungus was cultured on rice, followed by extraction and bioactivity-guided fractionation. Feature-Based Molecular Networking (FBMN) analysis of the LC-MS/MS data identified a cluster that correlated with antifungal activity. This led to the isolation of seven cytochalasin derivatives, four known derivatives, cytochalasin A (1), B (2), F (3), and deoxaphomin (4) and three new analogues of cytochalasin A, cytochalasin A1 (5), A2 (6); and A3 (7). The structural characterization was performed using 1 & 2D NMR and HRMS, and their absolute configuration was established using electronic circular dichroism. Antifungal evaluation of all the compounds isolated showed that cytochalasins A and F exhibited strong activity against B. cinerea (MICs=3.125 μg/mL and 6.25 μg/mL, respectively). The results obtained illustrate the potential of alpine plant endophytes as promising sources of bioactive compounds. Publication History Article published online: 05 March 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany