New and bioactive natural products from an endophyte of Panax notoginseng

Abstract

Five new derivatives of macrolide antibiotic Brefeldin A (BFA, 6), named as Brefeldin E1–E5 (1–5), along with Brefeldin A 7-O-acetate (7), mycotoxins (8–9) and mangrovamides A (10) were produced by an endophytic fungus, Penicillium sp., which was isolated from the healthy root of Panax notoginseng. The structures of 1–5 were established on the basis of their spectroscopic data, while the absolute configurations were assigned using a modified Mosher's method. All compounds were evaluated for their cytotoxic, antiviral and antimicrobial activities. Compounds 1–5 and 8–10 displayed low or moderate cytotoxicity against a panel of cancer cell lines. Compounds 1, 2, 4, 5, and 8–10 showed moderate antimicrobial activity. Compound 6 showed strong anticancer and antiviral properties. Additionally, it demonstrated broad-spectrum activity against human pathogenic bacteria and fungal pathogens that can cause root-rot disease in Panax notoginseng, including Escherichia coli, Staphylococcus aureus, Bacillus cereus, Klebsiella pneumonia, Candida albicans, Fusarium solani, Cylindrocarpon didynum and Alternaria panax. Compound 7, which could be mediated by 6 through the acetylation at the 7-hydroxyl, showed similar bioactivities to compound 6. Further studies of the cellular mechanism of compounds 6 and 7 showed that they arrested HepG2 cells at the S phase. Due to the similarities in the basic carbon skeleton and the chemical construction correlations between compounds 1–7, the plausible biosynthetic pathway of the BFA series of compounds has been proposed and their structure–activity relationships are also discussed.