De Leo_2018_Fitoterapia_130_251

As a part of our ongoing research program on compounds from higher plants with lactate dehydrogenase (LDH) and monoacylglycerol lipase (MAGL) inhibitory activities, three new neoclerodane diterpene 12-deacetylsplendidin C (1), pseudorosmaricin (2), and 2-dehydroxysalvileucanthsin A (3) along with six known compounds were isolated from Salvia pseudorosmarinus aerial part extracts. Their structures were determined by spectroscopic and spectrometric techniques including 1D- and 2D NMR, and MS analyses. The isolated diterpenes were assayed for their inhibitory activity on LDH5 and MAGL, two enzymes covering key roles in the peculiar energetic metabolism of malignant tumours. All the assayed diterpenes showed negligible activity on LDH5, whereas the known jewenol A (4) displayed a moderate inhibition activity on MAGL, showing an IC50 value of 46.8muM and it proved to be a reversible MAGL inhibitor. Docking and molecular dynamic simulation studies where thus performed to evaluate the binding mode of 4 within MAGL.