Novel Diterpenoids From Salvia rosmarinus Reveal a Compound With Antiproliferative and Antioxidant Activities.

Four previously undescribed diterpenoids (1-4) were isolated from the leaves of Salvia rosmarinus and characterized as 18-hydroxycarnosol (1), 18-acetoxyrosmanol (2), 18-acetoxycarnosol (3), and 18-acetoxy-7-O-methylrosmanol (4). Furthermore, nine known compounds, including carnosol (5), rosmanol (6), 7-O-methylacacetin (7), salvigenin (8), hispidulin (9), cirsimaritin (10), (1S,4S)-p-menth-2-ene-1,4-diol (11), 3,4,5-trimethoxycinnamyl alcohol (12), and vanillic acid (13) were also isolated. The structure of the new compounds was established primarily through the analysis of 1D and 2D nuclear magnetic resonance (NMR) experiments and high-resolution mass spectrometry by direct analysis in real time technique (HRMS DART). The absolute configuration of 1 and 2 was established by DP4+ analysis and comparison between experimental and theoretical electronic circular dichroism (ECD) spectra. The antiproliferative activity was evaluated against a panel of cancer cell lines and one normal cell line. Compounds 1 and 5 exhibited IC50 values of 10.77 ± 1.4 and 10.19 ± 0.4 μM, respectively, against a leukemia cell line, K562, and 25.27 ± 2.5 and 37.40 ± 3.7 μM, respectively, against the noncancerous cell line COS-7. Compound 7 exhibited IC50 values of 9.36 ± 0.1 μM against a glioblastoma cell line, U251, and 15.21 ± 1.7 μM against a prostate cell line, PC-3. The antioxidant activity of compound 1 was evaluated by its ability to scavenge the free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the inhibition of lipid peroxidation by the Thiobarbituric Acid Reactive Substances assay (TBARS), with IC50 of 25.50 ± 0.29 and 6.51 ± 0.09 μM, respectively. These results highlight the importance of S. rosmarinus being the subject of further chemical and biological studies.