Cytochalasins from the Sponge-Derived Fungus <i>Aspergillus templicola</i> and Their Biological Activities

Guided by biosynthetic gene cluster analysis, fractionation of the fermentation extract of <i>Aspergillus templicola</i> from the sponge <i>Agelas</i> sp. led to the isolation of nine new cytochalasins, named colachalasins A-I (<b>1</b>-<b>9</b>), along with four known cytochalasins (<b>10</b>-<b>13</b>). The structures of <b>1</b>-<b>9</b> were elucidated using spectroscopic data and single-crystal X-ray diffraction. Structurally, compound <b>2</b> is characterized by an open 12-carbon chain unprecedented among the cytochalasins. Compounds <b>1</b>-<b>3</b> demonstrated moderate protective effects against alcohol-induced hepatic damage in zebrafish assays. Compound <b>11</b> exhibited potent anti-inflammatory activity by inhibiting the expression of IKKβ, STAT3, TNF-α, IL-1β, NF-κB, NLRP3, IL-6, and MyD88 while enhancing the expression of IL-4 and Nrf2 in zebrafish assays. Additionally, compound <b>7</b> showed significant cytotoxicity against NCI-H446 cell lines, with an IC₅₀ value of 0.67 μM, and induced apoptosis in a dose-dependent manner.