The Identification of Perillyl Alcohol Glycosides with Improved Antiproliferative Activity
نویسندگان
چکیده
A facile route to perillyl alcohol (POH) differential glycosylation and the corresponding synthesis of a set of 34 POH glycosides is reported. Subsequent in vitro studies revealed a sugar dependent antiproliferative activity and the inhibition of S6 ribosomal protein phosphorylation as a putative mechanism of representative POH glycosides. The most active glycoside from this cumulative study (4'-azido-d-glucoside, PG9) represents one of the most cytotoxic POH analogues reported to date.
منابع مشابه
Synthesis and antiproliferative effects of amino-modified perillyl alcohol derivatives.
Two series of amino-modified derivatives of (S)-perillyl alcohol were designed and synthesized using (S)-perillaldehyde as the starting material. These derivatives showed increased antiproliferative activity in human lung cancer A549 cells, human melanoma A375-S2 cells and human fibrosarcoma HT-1080 cells comparing with that of (S)-perillyl alcohol. Among these derivatives, compounds VI5 and VI...
متن کاملInduction of the apoptosis-promoting protein Bak by perillyl alcohol in pancreatic ductal adenocarcinoma relative to untransformed ductal epithelial cells.
Perillyl alcohol has antitumor activity toward pancreas and other cancers with low toxicity. Here, we have investigated the mechanism of action responsible for the differential sensitivity of malignant versus non-malignant pancreatic cells to the drug. We report that the rate of apoptosis is over 6-fold higher in perillyl alcohol-treated pancreatic adenocarcinoma cells than in untreated cells, ...
متن کاملPerillyl alcohol inhibits a calcium-dependent constitutive nuclear factor-kappaB pathway.
The cell death induced by the monoterpene anticancer agent perillyl alcohol correlates to the increased expression of certain proapoptotic genes known to influence cell survival. Whereas sequence-specific DNA-binding factors dictate the expression patterns of genes through transcriptional regulation, those transcriptional factors influencing constitutive cell survival with perillyl alcohol trea...
متن کاملDiscovery of new biocatalysts for the glycosylation of terpenoid scaffolds.
The synthesis of terpenoid glycosides typically uses a chemical strategy since few biocatalysts have been identified that recognise these scaffolds. In this study, a platform of 107 recombinant glycosyltransferases (GTs), comprising the multigene family of small molecule GTs of Arabidopsis thaliana have been screened against a range of model terpenoid acceptors to identify those enzymes with hi...
متن کاملPerillyl Alcohol Inhibits Breast Cell Migration without Affecting Cell Adhesion
The monoterpene d-limonene exhibits chemotherapeutic and chemopreventive potential in breast cancer patients. D-limonene and its related compounds, perillyl alcohol and perillyl aldehyde, were chosen as candidate drugs for application in a screen for nontoxic inhibitors of cell migration. Using the nontumorigenic human breast cell line MCF-10A, we delineated the toxicity as greatest for the per...
متن کامل