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.
In our continuous chemical investigation on the marine-derived fungus Dichotomomyces cejpii F31-1, two new polyketides dichocetides B-C (1, 2), two new alkaloids dichotomocejs E-F (3, 4), and three known fumiquinozalines: scequinadoline A (5), quinadoline A (6), and scequinadoline E (7) were discovered from the culture broth and the mycelium in the culture medium, by the addition of l-tryptophan and l-phenylalanine. Their chemical structures were established by one dimensional (1D), two dimensional (2D) nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HR-MS) data. Among them, scequinadoline A (5) exhibited significant inhibitory activity against dengue virus serotype 2 production by standard plaque assay, equivalent to the positive control andrographlide. Scequinadoline A (5) possesses the potential for further development as a dengue virus inhibitor.
To investigate the influence of reactive oxygen species (ROS) on the secondary metabolites of the marine-derived fungus Dichotomomyces cejpii F31-1, hydrogen peroxide (H2O2) was added to the GPY culture medium. The HPLC chromatogram of the EtOAc extract of the culture broth was distinct from that of the H2O2 free GPY medium. Further study of the metabolites in the GPY medium with H2O2 resulted in the discovery of eight known compounds. Among them, (22E)-5α, 8α-epidioxyergosta-6, 22-dien-3β-ol (2) and ergosta-4,6,8(14),22-tetraene-3-one (3) were present in the highest concentration, while diketopiperazines are abundant in the H2O2 free medium. Additionally, a new compound, dichocetide D (1) containing a chlorine element and a known ergosterol (10) were isolated from the H2O2 free medium. (22E)-5α, 8α-epidioxyergosta-6, 22-dien-3β-ol (2) exhibited moderate cytotoxic activity against human prostate cancer cell line LNCaP-C4-2B.
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