Targeted discovery of oxygen-bridged sesquiterpenes from Cinnamomum migao by MS/MS-based molecular networking and...

Five previously undescribed oxygen-bridged sesquiterpenes (cinnamigones D-H), along with three known analogs, were isolated from the fruits of Cinnamomum migao using an MS/MS-based molecular networking strategy. Their structures were unambiguously elucidated through comprehensive spectroscopic analyses, including HRESIMS, X-ray crystallography, electronic circular dichroism calculations, and comparisons with existing literature data. All isolated compounds feature an oxygen-bridged structural units and a tricyclic framework. In particular, cinnamigone E (2) possesses a rare 6/7/6 tricyclic ring system, with the ring A being a benzene ring. The neuroprotective potential of these compounds was assessed using the N-methyl-d-aspartate (NMDA)-induced injury model in PC12 cells. Compounds 2 and 3 exhibited moderate neuroprotective activity against NMDA-induced neurotoxicity. Furthermore, molecular docking studies revealed that compound 2 bind to the active site of the NMDA receptor through hydrogen bonding and hydrophobic interactions.