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

Journal of Natural Products
Chan-Juan LiWen-Jian Lan

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 s...Continue Reading

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Citations

Apr 14, 2021·Journal of Investigative Medicine : the Official Publication of the American Federation for Clinical Research·Behnam MahdaviElahe Talebi
May 7, 2021·Natural Product Research·Qi GuoHou-Jin Li
Jul 14, 2021·Journal of Asian Natural Products Research·Huan-Nan WangZhen Zhang

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