ePrints

Inhibition of protein prenylation by metabolites of limonene

Lookup NU author(s): Dr Ian HardcastleORCiD

Downloads

Full text for this publication is not currently held within this repository. Alternative links are provided below where available.

Abstract

The monoterpenes limonene and perillyl alcohol are undergoing clinical evaluation in cancer patients. In this paper, we report the chemical synthesis, characterisation, and quantitation in patients’ plasma of a novel human metabolite of limonene, which is identified as an isomer of perillic acid. The synthesis of R-perillic acid is also described, because previous reports on the activity of perillic acid against isoprenylation enzymes refer to the S-enantiomer, although it is the R-enantiomer which is the metabolite of R-limonene. The above monoterpenes, with several related compounds, were assayed for inhibitory activity towards the isoprenylation enzymes in rat brain cytosol. Although R- and S-limonene are only weak inhibitors of the isoprenylation enzymes, their major metabolites, perillic acid and perillyl alcohol, are more potent inhibitors, with ₅₀ values in the low mM range. The metabolites possess greater activity towards the geranylgeranyltransferase type I enzyme than farnesyltransferase, while the novel metabolite displays ₅₀ values similar to those of perillic acid suggesting that it may contribute to the in vivo activity of limonene.

Publication metadata

Author(s): Hardcastle IR, Rowlands MG, Moreno BarberA, Grimshaw RM, Mohan MK, Nutley BP, Jarman M

Publication type: Article

Publication status: Published

Journal: Biochemical Pharmacology

Year: 1999

Volume: 57

Issue: 7

Pages: 801-809

Print publication date: 15/02/1999

ISSN (print): 0006-2952

ISSN (electronic): 1873-2968

Publisher: Elsevier Inc.

URL: http://dx.doi.org/10.1016/S0006-2952(98)00349-9

DOI: 10.1016/S0006-2952(98)00349-9

Altmetrics

Share