Isolation and Difference in Anti-Staphylococcus aureus Bioactivity of Curvularin Derivates from Fungus Eupenicillium sp

With the anti-microbial and anti-tumor composite screening model, bioassay-guided fractionation led to the isolation of two structurally related bioactive compounds, curvularin and αβ-dehydrocurvularin, from ethyl acetate extract of Eupenicillium sp. associated with marine sponge Axinella sp. Further study on the structure-activity relationship demonstrated that both compounds exhibited differences in bioactive profiles which are highly associated with their minor structural differences. Both curvularin and αβ-dehydrocurvularin have similar level of anti-fungal and anti-tumorous activity, while αβ-dehydrocurvularin is active against Staphylococcus aureus with a minimal inhibitory concentration of 375 μg/ml but curvularin does not. No detectable activity against Gram-negative bacteria such as Escherichia coli and Pseudomonas aeruginosa exists for both compounds. It is suggested that the partial planar backbone structure, due to the conjugation of π electrons in the presence of a 3,4-double bond and the carbonyl group at position C-2 in αβ-dehydrocurvularin, acts as a key factor for the inhibition of S. aureus, a Gram-positive low G + C bacteria that are often the hospital-acquired and/or community-acquired pathogen.