Cytotoxic activity of diterpenes and extracts of Juniperus brevifolia.

The hexane, dichloromethane, acetone and ethanol extracts of the leaves, bark and wood of Juniperus brevifolia were subjected to screening against human tumour cells lines from the cervix (HeLa) and larynx (Hep-2) in two different stages of the cell cycle. The dichloromethane and the chloroform-soluble portions of the acetone extracts of the leaves were active against both tumour cell lines. Chemical investigation of one of the most active extracts (dichloromethane extract from leaves) by preparative chromatography afforded compounds 1-10. Among these, compounds 1-3 were isolated for the first time from the Juniperus genus (18-hydroxyferruginol, 6,7-dehydrototarol and 7alpha-hydroxytotarol) while 4 and 5 are rare as natural products corresponding to (E)- and (Z)-isomers of 8alpha-hydroxy-labda-13(16),14-dien-19-yl-coumarate, respectively. The structures of all compounds were established based on various spectral data. The cytotoxic activity was evaluated for the first time for compounds 1-5 against HeLa and Vero cell lines in lag and log phases of growth. Compound 5 was shown to be active and selective to HeLa in the log phase.