Sclerotiamides C–H, Notoamides from a Marine Gorgonian-Derived Fungus with Cytotoxic Activities

Bioassay-guided fractionation in
association with LC-MS and NMR
detection led to the isolation of six new alkaloids, sclerotiamides
C–H (1–6), from the marine
gorgonian-derived fungus Aspergillus sclerotiorum LZDX-33-4. Their structures were determined from extensive spectroscopic
data, including ECD data and single-crystal X-ray diffraction analysis
for configurational assignments. Sclerotiamides C (1)
and D (2) are notoamide-type alkaloids with the incorporation
of a unique 2,2-diaminopropane unit, and sclerotiamides E (3) and F (4) are unprecedented notoamide hybrids with
a new coumarin unit. Sclerotiamide H (6) represents a
new highly oxidized notoamide scaffold. Sclerotiamides C and F showed
significant inhibition against a panel of tumor cell lines with IC50 values ranging from 1.6 to 7.9 μM. Sclerotiamide C
induces apoptosis in HeLa cells by arresting the cell cycle, activating
ROS production, and regulating apoptosis-related proteins in the MAPK
signaling pathway. The present study extends the scaffold diversity
of the notoamides and provides a potential lead for the development
of a cytotoxic agent.