Rapid discovery of two unprecedented meroterpenoids from Daphne altaica Pall. using molecular networking integrated with MolNetEnhancer and Network Annotation Propagation

Under the guidance of the approach which integrates molecular networking, MolNetEnhancer and Network Annotation Propagation (NAP), daphnaltaicanoids A and B (1 and 2) with unprecedented 9-oxa-tetracyclo[6.6.1.02,6.08,13]pentadecane and tetracyclo[5.3.0.12,5.24,11]tridecane central frameworks were isolated from Daphne altaica Pall., representing two types of unparalleled meroterpenoid cores. Their structures were elucidated by extensive spectroscopic analysis, nuclear magnetic resonance (NMR) calculations, DP4+ analysis and electronic circular dichroism (ECD) calculations. The plausible biosynthetic pathways for 1 and 2 were postulated. Biologically, 2 exerted potent neuroprotective activities which were superior to trolox at 12.5 and 25 µmol/L. Moreover, 1 and 2 exhibited more noticeable acetylcholinesterase inhibitory activities than donepezil. Molecular docking simulations were performed to explore the intermolecular interaction of compounds 1 and 2 with acetylcholinesterase. The bioactivity evaluation results highlight the prospects of 1 and 2 as a novel category of neurological agents.