Τίτλος:
Enzymatic synthesis of perillyl alcohol derivatives and investigation of their antiproliferative activity
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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.
Συγγραφείς:
Xanthakis, E.
Magkouta, S.
Loutrari, H.
Stamatis, H.
Roussos, C.
Kolisis, F.N.
Περιοδικό:
Biocatalysis and Biotransformation
Λέξεις-κλειδιά:
Anti-angiogenic activity; Anti-tumor; Antiproliferative activities; Antitumor growth activity; Biosynthetic pathway; Chemopreventive; Conversion yield; Enzymatic glucosylation/acylation; Enzymatic reaction; Enzymatic synthesis; Fatty esters; Glucosidase; Glucosylation; Hydroxyl groups; Laurate; Lewis lung carcinomata; Lipase B from Candida antarctica; Low-water systems; Monoterpene; Perillyl alcohol; Physicochemical property; Phytochemicals; Proliferation activity; Terpenoid, Cell membranes; Cell proliferation; Esterification; Glucose, Esters, antineoplastic agent; beta glucosidase; glucose; lauric acid derivative; lipase B; perillyl alcohol; perillyl glucoside; perillyl glucoside lauric ester; terpene; unclassified drug, almond; animal cell; antineoplastic activity; article; biocatalyst; biotransformation; Candida antarctica; concentration response; controlled study; drug structure; drug synthesis; enzyme kinetics; esterification; glycosylation; growth inhibition; Lewis carcinoma; mouse; nonhuman; process optimization, Candida antarctica; Prunus dulcis
DOI:
10.1080/10242420902811089
