posted on 2020-03-04, 18:41authored byChan-Juan Li, Pei-Nan Chen, Hou-Jin Li, Taifo Mahmud, Dong-Lan Wu, Jun Xu, Wen-Jian Lan
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.