Sesquiterpenes from the leaves of Laurus nobilis L.
Ten sesquiterpenes, together with 12 known compounds were isolated from leaves of Laurus nobilis L. Based on spectroscopic analyses, the 10 compounds were determined to be eudesmane lactones and their corresponding methyl esters. Most of these compounds exhibited moderate-to-significant cytotoxicity towards K562 leukemia cells. One compound had a higher cytotoxicity than doxorubicin, while other compounds had moderate to no activity.
Cytotoxicity of South-African medicinal plants towards sensitive and multidrug-resistant cancer cells.
ETHNOPHARMACOLOGICAL RELEVANCE
Traditional medicine plays a major role for primary health care worldwide. Cancer belongs to the leading disease burden in industrialized and developing countries. Successful cancer therapy is hampered by the development of resistance towards established anticancer drugs.


AIM
In the present study, we investigated the cytotoxicity of 29 extracts from 26 medicinal plants of South-Africa against leukemia cell lines, most of which are used traditionally to treat cancer and related symptoms.


MATERIAL AND METHODS
We have investigated the plant extracts for their cytotoxic activity towards drug-sensitive parental CCRF-CEM leukemia cells and their multidrug-resistant P-glycoprotein-overexpressing subline, CEM/ADR5000 by means of the resazurin assay. A panel of 60 NCI tumor cell lines have been investigated for correlations between selected phytochemicals from medicinal plants and the expression of resistance-conferring genes (ABC-transporters, oncogenes, tumor suppressor genes).


RESULTS
Seven extracts inhibited both cell lines (Acokanthera oppositifolia, Hypoestes aristata, Laurus nobilis, Leonotis leonurus, Plectranthus barbatus, Plectranthus ciliates, Salvia apiana). CEM/ADR5000 cells exhibited a low degree of cross-resistance (3.35-fold) towards the L. leonurus extract, while no cross-resistance was observed to other plant extracts, although CEM/ADR5000 cells were highly resistant to clinically established drugs. The log10IC50 values for two out of 14 selected phytochemicals from these plants (acovenoside A and ouabain) of 60 tumor cell lines were correlated to the expression of ABC-transporters (ABCB1, ABCB5, ABCC1, ABCG2), oncogenes (EGFR, RAS) and tumor suppressors (TP53). Sensitivity or resistance of the cell lines were not statistically associated with the expression of these genes, indicating that multidrug-resistant, refractory tumors expressing these genes may still respond to acovenoside A and ouabain.


CONCLUSION
The bioactivity of South African medicinal plants may represent a basis for the development of strategies to treat multidrug-resistant tumors either by phytotherapeutic approaches with whole plant preparations or by classical drug development with isolated compounds such as acovenoside A or ouabain.
Advanced Practical Organic Chemistry
General Introduction. Safety. Keeping Records of Laboratory Work. Equipping the Laboratory and the Bench. Purification and Drying of Solvents. Reagents: Preparation, Purification and Handling. Gases. Vacuum Pumps. Carrying out the Reaction. Working up the Reaction. Purification. Small Scale Reactions. Large Scale Reactions. Special Procedures. Characterization. Trouble Shooting. The Chemical Literature. Appendices. Index.