Spinulactones A–F: Bioactive Drimane-Type Sesquiterpenes from the Endophytic Penicillium spinulosum 9-1

Eight drimane-type sesquiterpenes, including six undescribed ones named spinulactones A-F (1-6), together with two known labdane-type diterpenoids (9 and 10) and a sterol (11), were isolated from the endophytic fungus Penicillium spinulosum 9-1. The structures and absolute configurations of the new compounds were characterized by extensive spectroscopic data, X-ray diffraction analysis, and electronic circular dichroism calculations. Compounds 1-5 feature a rare spiro β-lactone moiety, with 4 and 5 additionally incorporating a distinctive nicotinic acid structural motif. Biological evaluation revealed that compounds 1, 5, 6, 10, and 11 exhibited antifungal activity against the phytopathogen Fusarium graminearum with MIC values ranging from 6.25 to 25 μg/mL. Additionally, compounds 3, 7, 9, and 10 demonstrated significant in vivo proangiogenic activity in transgenic zebrafish. Compound 3 also displayed obvious antigastric aging effect in vitro. This study expanded the structural diversity of drimane-type sesquiterpenes and provided potential leads for agricultural and pharmaceutical applications.