Royleanone

Abietane diterpenes induce cytotoxic effects in human pancreatic cancer cell line MIA PaCa-2 through different modes of action.[Pubmed:22436445]

Phytochemistry. 2012 Jun;78:107-19.

Abietane diterpenes, especially those containing quinone moieties, are often reported to have cytotoxic effects on cancer cell lines. They deserve greater attention because several cancer chemotherapeutic agents also possess the quinone structural feature. To date, very little is known about their cytotoxic molecular modes of action. In the present study, five diterpenes, 7 alpha-acetoxyRoyleanone, horminone, Royleanone, 7-ketoRoyleanone and sugiol which have been previously isolated from the medicinal plant Peltodon longipes were shown to possess cytotoxic activity against the human pancreatic cancer cell line MIA PaCa-2. 7 alpha-AcetoxyRoyleanone, horminone and Royleanone were demonstrated to possess alkylating properties using the nucleophile 4-(4-nitrobenzyl)pyridine. However, no clear correlation between the alkylating properties and cytotoxicity of these diterpenes was observed. Furthermore, the relaxation activity of human DNA topoisomerases I and II was found to be influenced by these compounds, with 7-ketoRoyleanone and sugiol being the most active. These two diterpenes preferentially inhibited topoisomerase I and exhibited lower IC(50) values than the classical topoisomerase I inhibitor camptothecin. Molecular docking studies revealed possible interactions of diterpenes with topoisomerase I, indicating that these compounds do not form the drug-enzyme-DNA covalent ternary complex as observed with camptothecin. A binding pocket located at the surface of the DNA-interaction site was proposed. Moreover, the ability of the five diterpenes to generate DNA-strand breaks in single cells was confirmed using the alkaline comet assay. As expected, these diterpenes also influenced cell cycle progression and arrested cells in different phases of the cell cycle, primarily the G1/G0 and S-phases. Interestingly, the diterpenes only exhibited a slight ability to induce apoptotic cell death and failed to generate intracellular reactive oxygen species. These results provide additional understanding of the cytotoxic effects of abietane diterpenes. Depending on their functional groups, we propose that abietane diterpenes utilise different mechanisms to induce cell death.

Bioactivity-guided study of antiproliferative activities of Salvia extracts.[Pubmed:21615011]

Nat Prod Commun. 2011 May;6(5):575-9.

The cytotoxic activities of the n-hexane, chloroform and aqueous methanolic fractions prepared from the methanolic extract of the leaves of 23 Salvia taxa were studied for their cell growth-inhibitory activity against human cervix adenocarcinoma (HeLa), skin carcinoma (A431) and breast adenocarcinoma (MCF7) cells using the MTT assay. The n-hexane fractions of six Salvia taxa (S. hispanica, S. nemorosa, S. nemorosa 1. albiflora, S. pratensis, S. recognita and S. ringens) and the chloroform fraction ofS. officinalis 1. albiflora produced over 50% growth inhibition of the skin carcinoma cell line. None of the tested extracts showed substantial (above 50%) antiproliferative effects against HeLa and MCF7 cells. S. ringens was the most powerful among the studied Salvia species with a 61.8% cell growth inhibitory activity on A431 cells. In the case of S. ringens, other plant parts were also tested for antiproliferative effect, and the highest activities were recorded for the root extract. This was subjected to bioactivity-guided fractionation, which yielded four abietane diterpenes (Royleanone, horminone, 7-O-methyl-horminone and 7-acetyl-horminone), one triterpene (erythrodiol-3-acetate) and beta-sitosterol. Horminone, 7-acetyl-horminone and erythrodiol-3-acetate displayed marked concentration-dependent antiproliferative effects, while Royleanone and 7-O-methyl-horminone produced weaker activities.

Antioxidant diterpenoids from the roots of Salvia barrelieri.[Pubmed:19402189]

Phytochem Anal. 2009 Jul-Aug;20(4):320-7.

INTRODUCTION: The phytochemical and biological studies carried out on Salvia species showed that their extracts and constituents have various biological activities. OBJECTIVE: The aim of this study was the isolation of diterpenoids from the roots of Salvia barrelieri Ettling and the determination of the antioxidant activity. METHODOLOGY: Chromatographic methods were used for fractionation and isolation, respectively. Structure elucidation was established by spectroscopic methods. Five antioxidant assays were performed. RESULTS: Three new abietane diterpenoids barreliol, Royleanone 12-methyl ether and 7-epi-salviviridinol, and six known diterpenoids, with a known dammarane triterpenoid, pyxinol were isolated. The absolute stereochemistry of pyxinol was confirmed by X-ray analysis. CONCLUSION: Taxodione exhibited the highest antioxidant activity among the tested compounds.