Clerodanes from Salvia pseudorosmarinus and their activity as inhibitors of monoacylglycerol lipase (MAGL)

As a part of our research program for characterization of the biological activity of Lamiaceae diterpenes, the aerial part extract of Salvia pseudorosmarinus Epling, a perennial shrub up to 150 cm high with purple flowers growing in Peruvian Ande at 3500-4000 m above sea level, were investigated [1]. Over 900 Salvia species are widely distributed in different regions around the world such as the Mediterranean area, Central Asia, Africa, and America, and secondary metabolites produced by these plants include mainly diterpenoids, having an abietane or clerodane skeleton, sesquiterpenoids, triterpenoids, flavonoids, and polyphenols [2]. Diterpenoids and phenolic derivatives isolated from different species showed antioxidant, anticoagulant, cytoprotective, antihypertensive, anti-fibrotic, anti-ischemia-reperfusion injury, antiviral and antitumor activities [3]. Three new and one known clerodane diterpenes were isolated from the chloroform extract of the plant, by means of flash Silica gel column chromatography and RP-HPLC. The structural characterization of all compounds was performed by spectroscopic analyses, including 1D and 2D NMR, and HRESIMS experiments. The isolated compounds were assayed for their inhibitory activity on two enzymes involved in the peculiar glycolytic or lipidic metabolism of cancer cells, human lactate dehydrogenase (LDH) and monoacylglycerol lipase (MAGL), respectively. All the compounds showed negligible activity on LDH, whereas the known clerodane jewenol A displayed a certain inhibition activity on MAGL, showing an IC50 value of 75.8 µM.