Antibacterial and ATP Synthesis Modulating Compounds from Salvia tingitana.

Angela Bisio,Mauro Giacomini,Anna M Schito,Francesca Pedrelli,Jakob K Reinhardt,Tiziano Tuccinardi,Francesco De Riccardis,Giulio Poli,Thomas Bürgi,Isabella Panfoli,Gian Carlo Schito,Nunziatina De Tommasi,Ombeline Danton,Matthias Hamburger,Daniela Calzia

doi:10.1021/acs.jnatprod.9b01024

Abstract

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.

Highlights

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
Given that the overall structure and energy transduction mechanism of the Ftype ATP synthases are well conserved from bacteria to mammalians,35−38 purified mammalian rod outer segments (OS) were used as a subcellular system, allowing the rapid assay of the modulating action of the isolated compounds on the ectopic FoF1-ATP synthase.39−41 the OS are composed of a stack of membranous disks, naturally sealed vesicles expressing the molecular machinery for the complete oxidation of glucose, thereby comprising the tricarboxylic acid cycle,42 and the five complexes of respiration
The 1H NMR data (Table 1) displayed signals corresponding to five methyls, two oxymethine groups, and two protons of trisubstituted olefinic moieties. 1H−1H COSY and 1D TOCSY measurements allowed establishment of the spin systems C-1− C-3, C-5−C-7, C-9−C-12, and C-14−C-16

Summary

Introduction

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.

Results

Conclusion