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Lookup NU author(s): Dr Ian HardcastleORCiD
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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.
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
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