Ergostanes and Cytochalasin From the Fruiting Bodies of Xylaria longipes Nitschke and Their Cytotoxicity Evaluation

Four ergostanes—ergosta‐7,22,24(28)‐trien‐3 β ‐ol ( 1 ), ergosta‐7,24(28)‐dien‐3‐one ( 2 ), ergosta‐7,22,24(28)‐trien‐3‐one ( 3 ), and ergosta‐4,6,8(14),22‐tetraen‐3‐one ( 4 )—and one cytochalasin, zygosporin D ( 5 ), were isolated from Xylaria longipes . Two compounds, 2 and 3, are novel but have a similar structure to Compound ( 1 ), except for the keto group at the C‐3 carbon and the C‐22 double bond being reduced. Compound 5 was the most active at a single‐dose concentration against the majority of breast cancer and CNS cell lines evaluated. The NCI COMPARE Analysis tool was used to investigate the mode of action of Compound 5 in one‐dose screening and revealed no correlations, suggesting that Compound 5 may have a novel mode of action. Compound 5 was further subjected to molecular docking studies, which revealed its potential to interact with multiple cancer drug targets, including vascular endothelial growth factor receptor‐2, cyclin‐dependent kinases 2 and 6, ATPase/AMP‐PNP domain, and antiapoptotic protein BCL‐2, with binding affinity scores of −8.23, −9.25, −9.99, −9.43, and −9.15 kcal/mol, respectively. This molecule was also predicted to have a high drug‐likeness and good ADMET properties. Additionally, the diversity of compounds isolated from this Xylaria species highlights its potential as a valuable source for drug leads.