Phenolic C-Glycosides and Aglycones from Marine-Derived Aspergillus sp. and Their Anti-Inflammatory Activities

Abstract

A chemical investigation of the secondary metabolites of a marine-derived Aspergillus sp. led to the isolation and characterization of 13 phenolic compounds, including 10 new compounds (1–10). Seven new compounds (1–7) are unusual phenolic C-glycosides, while the other new compounds (8–10) are structurally related aglycones. The chemical structures of these new compounds were elucidated by 1D and 2D NMR and HRESIMS spectroscopic analyses. The absolute configurations of these new C-glycosides were determined by comparison of experimental electronic circular dichroism spectra with those of calculated ones. In addition, the anti-inflammatory activities of these compounds were evaluated, and compound 9 significantly inhibited nitric oxide production with an IC50 value of 6.0 ± 0.5 μM in lipopolysaccharide-induced RAW264.7 cells. Moreover, compound 9 also showed anti-inflammatory activity by inhibiting the NF-κB-activated pathway.

Arenicolins: C-Glycosylated Depsides from Penicillium arenicola

“…isolate has also recently appeared. 19 1 H and 13 C NMR shift assignments for relevant portions of all of these compounds match very well with those of 1 and 2, further supporting the structure assignments.…”

“…Verification of the absolute configuration of the C -glucopyranosyl unit found in both 1 and 2 was not attainable by hydrolytic methods, but as is the presumption with most molecules containing such a unit, it is proposed to be derived from d -glucose. A recent report suggested the use of electronic circular dichroism (ECD) to verify such assignments in similar, but somewhat simpler cases than structure 2 . Despite the somewhat variable NMR signal behavior of 2 in solution, we explored application of this method.…”

“…An additional report of carnemycins and several closely related metabolites from another marine-derived Aspergillus sp. isolate has also recently appeared …”

“…Efforts to obtain a degradation product of 1 corresponding to the cyclohexenone moiety by acid or base hydrolysis were unsuccessful. Verification of the absolute configuration of the C-glucopyranosyl unit found in both 1 and 2 was not attainable by hydrolytic methods, but as is the presumption with most molecules containing such a unit, 19 it is proposed to be derived from D-glucose. A recent report suggested the use of electronic circular dichroism (ECD) to verify such assignments in similar, but somewhat simpler cases than structure 2.…”

“…A recent report suggested the use of electronic circular dichroism (ECD) to verify such assignments in similar, but somewhat simpler cases than structure 2. 19 Despite the somewhat variable NMR signal behavior of 2 in solution, we explored application of this method. Like the simpler literature examples (which lack the second, substituted C-1′−C7′ aromatic ring unit) and the calculated spectra published for truncated versions thereof, the ECD curve for 2 showed a positive Cotton effect near 300 nm and a negative trend below 250 nm.…”