?-Glucosidase Inhibitors From the Coral-Associated Fungus Aspergillus terreus.

ABSTRACT: Nine novel butenolide derivatives, including four pairs of enantiomers, named (±)-asperteretones A-D (1a/1b-4a/4b), and a racemate, named asperteretone E (5), were isolated and identified from the coral-associated fungus Aspergillus terreus. All the structures were established based on extensive spectroscopic analyses, including HRESIMS and NMR data. The chiral chromatography analyses allowed the separation of (±)-asperteretones A-D, whose absolute configurations were further confirmed by experimental and calculated electronic circular dichroism (ECD) analysis. Structurally, compounds 2-5 represented the first examples of prenylated ?-butenolides bearing 2-phenyl-3-benzyl-4H-furan-1-one motifs, and their crucial biogenetically related metabolite, compound 1, was uniquely defined by an unexpected cleavage of oxygen bridge between C-1 and C-4. Importantly, (±)-asperteretal D and (4S)-4-decarboxylflavipesolide C were revised to (±)-asperteretones B (2a/2b) and D (4), respectively. Additionally, compounds 1a/1b-4a/4b and 5 were evaluated for the ?-glucosidase inhibitory activity, and all these compounds exhibited potent inhibitory potency against ?-glucosidase, with IC50 values ranging from 15.7 ± 1.1 to 53.1 ± 1.4 ?M, which was much lower than that of the positive control acarbose (IC50 = 154.7 ± 8.1 ?M), endowing them as promising leading molecules for the discovery of new ?-glucosidase inhibitors for type-2 diabetes mellitus treatment.

SUBMITTER: Liu M 

PROVIDER: S-EPMC6146087 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature