In this study, the fungus Aspergillus felis (strain UFMGCB 8030) was isolated from rocks in the Atacama Desert, Chile. Its CH2Cl2 extract exhibited antifungal activity (MIC of 1.9 μg/mL) against Paracoccidioides brasiliensis (Pb18), which is the etiological agent for paracoccidioidomycosis. The crude extract was purified, and a new cytochalasin derivative, cytochalasin Z15E (1), and one ardeemin derivative, 5-N-acetyl-8-β-isopropyl-ardeemin (4), in addition to five known secondary metabolites, rosellichalasin (2), cytochalasin E (3), gancidin (5), pseurotin A1 (6), and 2,4-dihydroxyacetophenone (7), were isolated. The structures of these compounds were confirmed by 1D and 2D NMR spectroscopy and HR-ESI⿿MS. Cytochalasin E was the most active compound with MIC an value of 3.6 μM, while the other isolated compounds exhibited weak antifungal activities (MIC values >100.0 μM).2021-01-01