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 IC 50 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.