Exploring Brominated Aromatic Butenolides from <i>Aspergillus terreus</i> EGF7-0-1 with Their Antifungal Activities

Fungal diseases could severely harm agricultural productions. To develop new antifungal agents, based on the Global Natural Products Social Molecular Networking, typical bromine isotope peak ratios, and ultraviolet absorptions, cultivation of the soft coral-derived endophytic fungi <i>Aspergillus terreus</i> EGF7-0-1 with NaBr led to the targeted isolation of 14 new brominated aromatic butenolides (<b>1</b>-<b>14</b>) and six known analogues (<b>15</b>-<b>20</b>). Their structures were elucidated by extensive spectroscopic analysis and quantum chemical calculations. Compounds <b>1</b>-<b>14</b> exhibited wildly antifungal activities (against <i>Colletotrichum gloeosporioides</i>, <i>Pestalotiopsis microspora</i>, <i>Fusarium oxysporum</i> f. sp. <i>cubense</i>, <i>Botrytis cinerea</i>, and <i>Diaporthe phoenicicola</i>). The bioassay results showed that compounds <b>1</b>-<b>14</b> exhibited excellent antifungal activities against <i>C. gloeosporioides</i>, with concentration for 50% of maximal effect (EC₅₀) values from 2.72 to 130.41 nM. The mechanistic study suggests that compound <b>1</b> may disrupt nutrient signaling pathways by reducing the levels of metabolites, such as carbohydrates, lipids, and amino acids, leading to an increase in low-density granules and a decrease in high-density granules in the cytoplasm, accompanied by numerous vacuoles, thereby inhibiting the growth of <i>C. gloeosporioides</i>. Monobrominated γ-butenolide <b>1</b> may be expected to exploit a novel agriculturally antifungal leading drug. Meanwhile, compound <b>M1</b> has conformed antifugual activities against <i>C. gloeosporioides</i> by papayas <i>in vivo</i>.