New Metabolite With Inhibitory Activity Against α-Glucosidase and α-Amylase From Endophytic Chaetomium globosum

An efficient bioactive tracking separation strategy based on liquid-liquid extraction and high-speed counter-current chromatography (HSCCC) was developed and used to isolate bioactive natural products from the endophytic fungus Chaetomium globosum residing in Ginkgo biloba. Using HSCCC, the novel metabolite chaetoglobol acid (1) as well as 11 known compounds (2-12), including 6 chlorinated azaphilones and 3 cytochalasans, were successfully isolated. The structure of compound 1 was elucidated through spectroscopic analyses and HRESIMS data. Compound 1 possesses a rare C₁₁-polyketide skeleton. All isolates were evaluated for their α-glucosidase and α-amylase inhibitory activities in vitro. Compound 1 showed high inhibition against α-glucosidase (IC₅₀ = 3.04 μM), 18-fold higher than that of acarbose (IC₅₀ = 54.74 μM), and also displayed moderate inhibitory activity against α-amylase (IC₅₀ = 22.18 μM). As the results indicated that 1 has inhibitory effects against both α-glucosidase and α-amylase, 1 may be a promising candidate for mediating type 2 diabetes.