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

Mengting Liu,Yongbo Xue,Weiguang Sun,Jianping Wang,Yonghui Zhang,Yongji Lai,Changxing Qi,Ling Shen,Junjun Liu,Zhengxi Hu

doi:10.3389/fchem.2018.00422

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 γ-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 α-glucosidase inhibitory activity, and all these compounds exhibited potent inhibitory potency against α-glucosidase, with IC50 values ranging from 15.7 ± 1.1 to 53.1 ± 1.4 μM, which was much lower than that of the positive control acarbose (IC50 = 154.7 ± 8.1 μM), endowing them as promising leading molecules for the discovery of new α-glucosidase inhibitors for type-2 diabetes mellitus treatment.

Highlights

Diabetes mellitus (DM) is one of the most serious chronic diseases with the ever-increasing incidence rates of obesity and aging of the general population throughout the world (Kopelman, 2000) In 2013, it was estimated that over 382 million people all over the world have DM and this number is predicted to increase up to 500 million in 2030, when this disease will be excepted to be the 7th leading cause of death (Lauritano and Ianora, 2016)
A good strategy to maintain the normal level of postprandial plasma glucose is to medicate in α-Glucosidase Inhibitors From Aspergillus terreus combination with dietary restriction and an exercise plan (Kim et al, 2008)
In our continuous search for chemically novel and bioactive secondary metabolites from marine fungi (Hu et al, 2014; Liu et al, 2018a,b; Yang et al, 2018), we focused our attention on a coral-associated fungus Aspergillus terreus

Summary

Introduction

Diabetes mellitus (DM) is one of the most serious chronic diseases with the ever-increasing incidence rates of obesity and aging of the general population throughout the world (Kopelman, 2000) In 2013, it was estimated that over 382 million people all over the world have DM and this number is predicted to increase up to 500 million in 2030, when this disease will be excepted to be the 7th leading cause of death (Lauritano and Ianora, 2016).

Results

Conclusion