Cytotoxic Activity of Diterpenes and Extracts of Juniperus brevifolia

Abstract

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 7α-hydroxytotarol) while 4 and 5 are rare as natural products corresponding to (E)- and (Z)-isomers of 8α-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.

Abbreviations

AB: acetone extract from bark

ALIC: chloroform-insoluble portion of the acetone extractfrom leaves

ALSC: chloroform-soluble portion of the acetone extract from leaves

AW: acetone extract from wood

DL: dichloromethane extract from leaves

DMSO: dimethyl sulfoxide

DW: dichloromethane extract from wood

EB: ethanol extract from bark

EL: ethanol extract from leaves

EW: ethanol extract from wood

HB: hexane extract from bark

HeLa: human carcinoma of the cervix

Hep-2: human carcinoma of the larynx

HL: hexane extract from leaves

Vero: African green monkey kidney cell line

Key words

Juniperus brevifolia - Cupressaceae - HeLa - Hep-2 - diterpenes

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