Abstract
Glioblastoma multiforme (GBM) is an aggressive brain tumor that correlates with short patient survival and for which therapeutic options are limited. Polyphenolic compounds, including caffeic acid phenethyl ester (CAPE, 1a), have been investigated for their anticancer properties in several types of cancer. To further explore these properties in brain cancer cells, a series of caffeic and ferulic acid esters bearing additional oxygens moieties (OH or OCH3) were designed and synthesized. (CAPE, 1a), but not ferulic acid phenethyl ester (FAPE, 1b), displayed substantial cytotoxicity against two glioma cell lines. Some but not all selected compounds derived from both (CAPE, 1a) and (FAPE, 1b) also displayed cytotoxicity. All CAPE-derived compounds were able to significantly inhibit 5-lipoxygenase (5-LO), however FAPE-derived compounds were largely ineffective 5-LO inhibitors. Molecular docking revealed new hydrogen bonds and π-π interactions between the enzyme and some of the investigated compounds. Overall, this work highlights the relevance of exploring polyphenolic compounds in cancer models and provides additional leads in the development of novel therapeutic strategies in gliomas.
Highlights
Glioblastoma multiforme (GBM) is the most frequent brain tumor diagnosed in adults and current standard of care, consisting of surgery, radiotherapy, and chemotherapy, translates to overall patient survival between 7 and 15 months [1]
Natural polyphenolic compounds derived from caffeic acidacid phenethyl ester (CAPE) (1a) have notably been linked to Natural polyphenolic compounds derived from CAPE (1a) have notably been linked to antioxidant antioxidant and radical scavenging properties [14]
We report the design, synthesis, and biological evaluation of CAPE
Summary
Glioblastoma multiforme (GBM) is the most frequent brain tumor diagnosed in adults and current standard of care, consisting of surgery, radiotherapy, and chemotherapy, translates to overall patient survival between 7 and 15 months [1]. Curcumin can inhibit glioma tumor growth in mouse xenograft models [13]. Such PI3K compounds provide starting pointsglioma in the tumor quest of identifying novel therapeutic agents and mTOR [12]. Curcumin can inhibit glioma mouse [13] Such compounds provide interesting startingtumor pointsgrowth in the in quest of xenograft identifyingmodels novel [13]. LT biosynthesis enzymes, supporting anti-LT therapy as promising anticancer strategy response to the need for targeting the LT biosynthesis pathway, studies have efficient inhibitors [22,23]. Synthesized compounds investigated in two glioma lines for their cytotoxic properties and for in their sensitizing to temozolomide (TMZ, 4), cell the for primary chemotherapeutic agent.
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