Synthesis of amphipathic derivatives of perillyl glucoside by lipase-catalysed esterification in non conventional media
Date Issued
September 10, 2008
Abstract
Perillyl alcohol (POH), is a plant secondary metabolite. It is found in small
concentrations in the essential oils of Chios mastic gum, lavendin, peppermint,
spearmint etc. Perillyl alcohol (POH) is a monoterpene with anticarcinogenic and
antitumor activity in murine tumor models and has been reported to possess
chemotherapeutic activity against malignancies. Perillyl glucoside is also a natural
compound contained in Perilla frutescens but no data about its biological activity have
ever been reported.
The studies of lipophilicity and hydrolysis in vitro of prodrugs verified that drugñ
saccharide derivatives had amphipathic properties and both lipophilic and amphipathic
drug derivatives had obvious controlled release characteristics. Some amphipathic
macromolecule drugs are designed for improving pharmaceuticals delivery properties
and generally used to enhance the permeability of cell membranes.
In the present study is demonstrated the enzymatic synthesis of a perillyl
glucoside fatty ester. In the first step, almond β- glucosidase catalyzed the glucosidation
of perillyl alcohol by reverse hydrolysis with β-glucose in a biphasic system. In the
second step, immobilised lipase from Candida antarctica (Novozym 435) was used in
organic media to catalyse the acylation of perillyl glucoside with a medium chain fatty
acid. The chemical structure of the products was determined by Mass Spectrometry
analysis (MS). The antiproliferative activity of perillyl glucoside and perillyl glucoside
fatty ester on LLC cells was investigated.
Acknowledgements:
This work has been funded by the project PENED 2003. The project is cofinanced 75%
of public expenditure through EC - European Social Fund, 25% of public expenditure
through Ministry of Development - General Secretariat of Research and Technology
and through private sector, under measure 8.3 of OPERATIONAL PROGRAMME
"COMPETITIVENESS" in the 3rd Community Support Programme.
concentrations in the essential oils of Chios mastic gum, lavendin, peppermint,
spearmint etc. Perillyl alcohol (POH) is a monoterpene with anticarcinogenic and
antitumor activity in murine tumor models and has been reported to possess
chemotherapeutic activity against malignancies. Perillyl glucoside is also a natural
compound contained in Perilla frutescens but no data about its biological activity have
ever been reported.
The studies of lipophilicity and hydrolysis in vitro of prodrugs verified that drugñ
saccharide derivatives had amphipathic properties and both lipophilic and amphipathic
drug derivatives had obvious controlled release characteristics. Some amphipathic
macromolecule drugs are designed for improving pharmaceuticals delivery properties
and generally used to enhance the permeability of cell membranes.
In the present study is demonstrated the enzymatic synthesis of a perillyl
glucoside fatty ester. In the first step, almond β- glucosidase catalyzed the glucosidation
of perillyl alcohol by reverse hydrolysis with β-glucose in a biphasic system. In the
second step, immobilised lipase from Candida antarctica (Novozym 435) was used in
organic media to catalyse the acylation of perillyl glucoside with a medium chain fatty
acid. The chemical structure of the products was determined by Mass Spectrometry
analysis (MS). The antiproliferative activity of perillyl glucoside and perillyl glucoside
fatty ester on LLC cells was investigated.
Acknowledgements:
This work has been funded by the project PENED 2003. The project is cofinanced 75%
of public expenditure through EC - European Social Fund, 25% of public expenditure
through Ministry of Development - General Secretariat of Research and Technology
and through private sector, under measure 8.3 of OPERATIONAL PROGRAMME
"COMPETITIVENESS" in the 3rd Community Support Programme.