Enzymatic synthesis of perillyl alcohol derivatives and investigation of their antiproliferative activity |
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Authors: | Epameinondas Xanthakis Sophia Magkouta Heleni Loutrari Haralambos Stamatis Charis Roussos |
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Affiliation: | 1. School of Chemical Engineering, National Technical University of Athens, Athens, Greece;2. G. P. Livanos and M. Simou Laboratories, Evangelismos Hospital, Department of Critical Care and Pulmonary Services, Medical School, University of Athens, Athens, Greece;3. Department of Biological Applications and Technologies, University of Ioannina, Ioannina, Greece |
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Abstract: | The monoterpene perillyl alcohol (POH), an intermediate in the plant terpenoid biosynthetic pathway, has well-established tumor chemopreventive and chemotherapeutic potential. We have previously shown that the primary hydroxyl group of POH is essential for its antitumor and anti-angiogenic activities. In the current study we present the enzymatic synthesis of two POH derivatives with different polar and hydrophobic characteristics, namely perillyl glucoside and perillyl glucoside fatty ester, through a two-step modification. Initial glucosylation of POH on its active hydroxyl group with D-(+)-glucose and subsequent esterification of the perillyl glucoside product with vinyl laurate were carried out using almond β-glucosidase and lipase B from Candida antarctica, respectively, in a low-water system. Optimization of enzymatic reactions was performed to achieve the highest possible conversion yields. The antitumor cell proliferation activity against mouse Lewis lung carcinoma cells was retained in both derivatives, although the perillyl glucoside ester showed greater inhibition than perillyl glucoside. Our results underline the feasibility of enzymatically producing novel bioactive analogs of phytochemicals displaying useful physicochemical properties. |
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Keywords: | Perillyl alcohol enzymatic glucosylation/acylation glucosidase lipase B antitumor growth activity |
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