Perillyl alcohol

Perillyl alcohol
(R)-(+)-Perillyl alcohol
(S)-(-)-Perillyl alcohol
Names
IUPAC name
(4-Isopropenyl-1-cyclohexen-1-yl)methanol
Identifiers
536-59-4
ChemSpider 10362
Jmol interactive 3D Image
PubChem 10819
Properties
C10H16O
Molar mass 152.24 g·mol−1
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Infobox references

Perillyl alcohol (IUPAC name: [4-(prop-1-en-2-yl)cyclohex-1-en-1-yl]methanol) and its precursor limonene are naturally occurring monocyclic terpenes derived from the mevalonate pathway in plants. Perillyl alcohol can be found in the essential oils of various botanicals, such as lavender, lemongrass, sage, and peppermint.[1] It has a number of manufacturing, household, and medical applications. For example, perillyl alcohol may be used as an ingredient in cleaning products and cosmetics,[2] and it has shown promise for inhalation therapy of patients with brain cancer.[3]

Biosynthesis

Perillyl alcohol is only produced by certain botanicals, not by animals or humans. It is a metabolite of limonene, which itself is formed from geranyl pyrophosphate in the mevalonate pathway. Conversion of limonene to perillyl alcohol is accomplished via hydroxylation by enzymes that belong to the superfamily of cytochrome P450 proteins. Perillyl alcohol can be metabolized further to perillaldehyde (perillyl aldehyde) and perillic acid. [4]

Cancer therapeutic activity

Based on promising results in animal experiments, the therapeutic activity of perillyl alcohol was subsequently tested in cancer patients.[5] It was formulated in soft gelatine capsules and orally administered to cancer patients several times a day for several months. However, such clinical trials in humans yielded disappointing results, also because the large number of capsules that had to be swallowed caused hard-to-tolerate intestinal side effects, causing many patients to withdraw from treatment due to unrelenting nausea, fatigue, and vomiting. As a result, efforts to treat cancer patients with perillyl alcohol in the form of capsules that had to be swallowed were abandoned and did not enter clinical practice. [6][7][8]

Intriguingly, clinical trials in Brazil explored an alternative way to give perillyl alcohol to cancer patients.[9] In order to avoid the severe intestinal side effects, perillyl alcohol was given via "sniffing", that is: the compound was administered via inhalation through the nose. Compared to oral delivery, the amount of perillyl alcohol that was inhaled was much smaller. Nonetheless, perillyl alcohol given via simple inhalation showed promising results in these brain cancer patients, and side effects were nearly non-existent. [10][11]

See also

References

  1. ↑ Crowell PL and Elson CE (2001). Isoprenoids, Health and Disease. In: Wildman REC, editors. Neutraceuticals and Functional Foods. Boca Raton, FL: CRC Press, LLC. pp. 31–53.
  2. ↑ Laszlo P (2007). Citrus: A History. Chicago, IL: University of Chicago Press.
  3. ↑ Chen TC, Da Fonseca CO, Schönthal AH (2015). "Preclinical development and clinical use of perillyl alcohol for chemoprevention and cancer therapy". American Journal of Cancer Research 5 (5): 1580–93. PMID 26175929.
  4. ↑ Mann, J. C.; Hobbs, J. B.; Banthorpe, D. V.; Harborne, J. B. (1994). Natural products: their chemistry and biological significance. Harlow, Essex, England: Longman Scientific & Technical. pp. 308–9. ISBN 0-582-06009-5.
  5. ↑ Bailey HH, Levy D, Harris LS, Schink JC, Foss F, Beatty P and Wadler S. "A phase II trial of daily perillyl alcohol in patients with advanced ovarian cancer: Eastern Cooperative Oncology Group Study E2E96". Gynecol Oncol. 85 (3): 464–8. doi:10.1006/gyno.2002.6647. PMID 12051875.
  6. ↑ Meadows SM, Mulkerin D, Berlin J, Bailey H, Kolesar J, Warren D and Thomas JP (2002). "Phase II trial of perillyl alcohol in patients with metastatic colorectal cancer". Int. J. Gastrointest. Cancer 32 (2–3): 125–8. doi:10.1385/ijgc:32:2-3:125. PMID 12794248.
  7. ↑ Liu G, Oettel K, Bailey H, Ummersen LV, Tutsch K, Staab MJ, Horvath D, Alberti D, Arzoomanian R, Rezazadeh H, McGovern J, Robinson E, DeMets D and Wilding G (2003). "Phase II trial of perillyl alcohol (NSC 641066) administered daily in patients with metastatic androgen independent prostate cancer". Invest. New Drugs 21 (3): 367–72. PMID 14578686.
  8. ↑ Bailey HH, Attia S, Love RR, Fass T, Chappell R, Tutsch K, Harris L, Jumonville A, Hansen R, Shapiro GR and Stewart JA (2008). "Phase II trial of daily oral perillyl alcohol (NSC 641066) in treatment-refractory metastatic breast cancer". Cancer Chemother. Pharmacol. 62 (1): 149–57. doi:10.1007/s00280-007-0585-6. PMID 17885756.
  9. ↑ da Fonseca CO, Schwartsmann G, Fischer J, Nagel J, Futuro D, Quirico-Santos T and Gattass CR (2008). "Preliminary results from a phase I/II study of perillyl alcohol intranasal administration in adults with recurrent malignant gliomas". Surg. Neurol. 70 (3): 259–66. doi:10.1016/j.surneu.2007.07.040. PMID 18295834.
  10. ↑ Da Fonseca CO, Simao M, Lins IR, Caetano RO, Futuro D and Quirico-Santos T (2011). "Efficacy of monoterpene perillyl alcohol upon survival rate of patients with recurrent glioblastoma". J. Cancer Res. Clin. Oncol. 137 (2): 287–93. doi:10.1007/s00432-010-0873-0. PMID 20401670.
  11. ↑ Da Fonseca CO, Teixeira RM, Silva JC, DE Saldanha da Gama Fischer, Meirelles OC, Landeiro JA and Quirico-Santos T (2013). "Long-term outcome in patients with recurrent malignant glioma treated with perillyl alcohol inhalation". Anticancer Res. 33 (12): 5625–5631. PMID 24324108.
This article is issued from Wikipedia - version of the Saturday, December 19, 2015. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.