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.