Potential Antidiabetic Fumiquinazoline Alkaloids from the Marine-Derived Fungus Scedosporium apiospermum F41-1

Abstract

Fumiquinazoline alkaloids have attracted much attention from medicinal and natural product chemists due to their interesting structures and biological potential. In this study, three new and 12 known fumiquinazoline alkaloids were isolated and characterized from the marine fungus Scedosporium apiospermum F41-1. The structures of the new compounds and their absolute configurations were determined using NMR spectroscopy, ECD, and OR calculations. The compounds were evaluated for their antidiabetic potential by determining their triglyceride-promoting activity using 3T3-L1 adipocytes. One of the new compounds, scequinadoline J (14), as well as scequinadolines D (9) and E (10), was found to promote triglyceride accumulation in 3T3-L1 cells. Scequinadoline D (9) demonstrated the most potent activity, with an EC50 value of 0.27 ± 0.03 μM. Quantitative polymerase chain reaction experiments suggested that scequinadoline D (9) acts through activation of the PPARγ pathway. It stimulated the mRNA expression of PPARγ, AMPKα, C/EBPα, LXRα, SCD-1, and FABP4. In addition, its triglyceride-promoting efficacy could be blocked by a double dose of the PPARγ antagonist GW9662. These results indicated that scequinadoline D (9) is a potent insulin sensitizer that targets adipocytes and may be useful for the treatment of type 2 diabetes mellitus after further investigation.

Isolation, Structural Characterization and Antidiabetic Activity of New Diketopiperazine Alkaloids from Mangrove Endophytic Fungus Aspergillus sp. 16-5c

“…The 1 H-1 H COSY spectrum of 6 showed cross-peaks that connect the aromatic protons from H-6 (δ H 7.73) through H-9 (δ H 8.14), while HMBC correlations from H-6 to C-10 (δ C 121.6), from H-9 to C-5 (δ C 128.2)/C-11 (δ C 161.8) suggested a quinazoline ring. The quinazoline ring was further fused with a pyrazine to form a tricyclic pyrazinoquinazolinedione [20], which was consistent with HMBC correlations from H-13 (δ H 5.37) to C-11/C-3 (δ C 151.4)/C-14 (δ C 171.8), from H-2 (δ H 5.71) to C-3/C-14. Moreover, the linkage between the para-substituted benzene ring and pyrazinoquinazolinedione moiety by C-15 was deduced based on HMBC correlations from H-13 to C-6, from H-17/H-19 to C-15 (Figure 2).…”

Natural Products Targeting Liver X Receptors or Farnesoid X Receptor

“…Scequinadoline D (69), an alkaloid derived from the marine fungus Scedosporium apiospermum F41-1, stimulated the mRNA expression of a series target genes, such as LXRα and PPARγ. It was found to facilitate TG accumulation with EC 50 values of 0.27 ± 0.03 μM as a potent insulin sensitizer targeting adipocytes and a promising potential for the treatment of T2D ( Li CJ. et al, 2020 ).…”

New Antiproliferative Compounds against Glioma Cells from the Marine-Sourced Fungus Penicillium sp. ZZ1750

“…The cyclotryprostatin [ 34 , 46 ], fumiquinazoline [ 35 , 46 , 47 , 48 ], and verruculogen [ 31 , 34 ] indole alkaloids were most frequently isolated from Aspergillus and Penicillium fungi. Some of them have reported antibacterial, antifungal, cytotoxic, and antidiabetic activities [ 48 , 49 ]. In this study, seven such known indole alkaloids (compounds 9 – 15 ) were obtained from the metabolites produced by the marine-sourced Penicillium fungus ZZ1750.…”