Antibacterial and ATP Synthesis Modulating Compounds from Salvia tingitana

A surface extract of the aerial parts of Salvia tingitana afforded a nor-sesterterpenoid ( 1 ) and eight new sesterterpenoids ( 2 -̵ 9 ), along with five known sesterterpenoids, five labdane and one abietane diterpenoid, one sesquiterpenoid, and four flavonoids. The structures of the new compounds were established by 1D and 2D NMR spectroscopy, HRESIMS, and VCD data and Mosher's esters analysis. The antimicrobial activity of compounds was evaluated against 30 human pathogens including 27 clinical strains and three isolates of marine origin for their possible implications on human health. The methyl ester of salvileucolide ( 10 ), salvileucolide-6,23-lactone ( 11 ), sclareol ( 15 ), and manool ( 17 ) were the most active against Gram-positive bacteria. The compounds were also tested for the inhibition of ATP production in purified mammalian rod outer segments. Terpenoids 10 , 11 , 15 , and 17 inhibited ATP production, while only 17 inhibited also ATP hydrolysis. Molecular modeling studies confirmed the capacity of 17 to interact with mammalian ATP synthase. A significant reduction of ATP production in the presence of 17 was observed in Enterococcus faecalis and E. faecium isolates.