Four previously undescribed diketopiperazines from marine fungus Aspergillus puniceus FAHY0085 and their effects on liver X receptor α

Abstract

Four previously undescribed diketopiperazine-type alkaloids including one oxepin-containing diketopiperazine-type alkaloid, oxepinamide L (1), three 4-quinazolinone alkaloids, puniceloids E-G (10–12), together with 12 known analogues, protuboxepin D (2), oxepinamides D-G, J-K and I (3–9), puniceloids B-D (13–15) and protubonine B (16), were isolated from the culture of the marine-derived fungus Aspergillus puniceus FAHY0085. The structures of the previously undescribed compounds were comprehensively elucidated by detailed interpretation of their NMR and HRESIMS data. Their absolute configurations were unambiguously determined by ROESY experiments, Marfey's method, calculated ECD experiments and single-crystal X-ray diffraction analysis. Compounds (3–4, 6–8, 14–15) were evaluated for their cytotoxic activity against HepG2, MCF-7, SW1116 and HeLa cells and compound 6 and 14 showed moderate cytotoxic activity against HeLa cells with IC50 49.61 ± 2.91 and 28.38 ± 1.57 μM, respectively. Compounds (1–8, 11–15) were screened for their transcriptional activation of liver X receptor α and compound 11 with known compounds 13–15 showed significant transcriptional activation of liver X receptor α with EC50 values in the range 2–50 μM.