Nine undescribed sesquiterpenoids from the aerial parts of Daphne penicillata: cyclooxygenase-2 inhibition, molecular docking, and molecular dynamics studies

Nine undescribed carotane sesquiterpenes and rare rearranged guaiane sesquiterpenoids (1-9), along with two known analogues (10-11), were obtained from the aerial parts of Daphne penicillata. Their structures and absolute configurations were determined by extensive spectroscopic analyses, NMR/ECD calculations, and single-crystal X-ray diffraction analysis. All the compounds were evaluated for anti-inflammatory and cytotoxic activities. The inhibitory effect of several active sesquiterpenoids against the cyclooxygenase-2 (COX-2) enzyme was also examined by an in vitro enzyme inhibition assay. Furthermore, molecular docking, molecular dynamics (MD) simulation, and binding free energy calculations were applied to further analyze the interactions, stability, and affinity, among which compounds 3 and 4 exhibited high binding affinities and stable binding to the active site of COX-2.