Cytochalasins from the Sponge-Derived Fungus Aspergillus templicola and Their Biological Activities

Guided by biosynthetic gene cluster analysis, fractionation of the fermentation extract of Aspergillus templicola from the sponge Agelas sp. led to the isolation of nine new cytochalasins, named colachalasins A-I (1-9), along with four known cytochalasins (10-13). The structures of 1-9 were elucidated using spectroscopic data and single-crystal X-ray diffraction. Structurally, compound 2 is characterized by an open 12-carbon chain unprecedented among the cytochalasins. Compounds 1-3 demonstrated moderate protective effects against alcohol-induced hepatic damage in zebrafish assays. Compound 11 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 7 showed significant cytotoxicity against NCI-H446 cell lines, with an IC₅₀ value of 0.67 μM, and induced apoptosis in a dose-dependent manner.