5-hydroxy-3-3--4--7-tetramethoxyflavone and chrysin

Selenium-containing chrysin (SeChry) and 3,7,3',4'-tetramethylquercetin (SePQue) derivatives were synthesized by a microwave-based methodology. In addition to their improvement in terms of DPPH scavenging and potential GPx-like activities, when tested in a panel of cancer cell lines both selenium-derivatives revealed consistently to be more cytotoxic when compared with their oxo and thio-analogues, evidencing the key role of selenocabonyl moiety for these activities. In particular, SeChry elicited a noteworthy cytotoxic activity with mean IC50 values 18- and 3-fold lower than those observed for chrysin and cisplatin, respectively. Additionally, these seleno-derivatives evidenced an ability to overcome cisplatin and multidrug resistance. Notably, a differential behavior toward malignant and nonmalignant cells was observed for SeChry and SePQue, exhibiting higher selectivity indexes when compared with the chalcogen-derivatives and cisplatin. Our preliminary investigation on the mechanism of cytotoxicity of SeChry and SePQue in MCF-7 human mammary cancer cells demonstrated their capacity to efficiently suppress the clonal expansion along with their ability to hamper TrxR activity leading to apoptotic cell death.

Topics: Antineoplastic Agents; Cell Line, Tumor; Cell Survival; Chemistry Techniques, Synthetic; Cisplatin; Drug Resistance, Multiple; Drug Resistance, Neoplasm; Drug Screening Assays, Antitumor; Flavonoids; Free Radical Scavengers; Humans; Inhibitory Concentration 50; Magnetic Resonance Spectroscopy; MCF-7 Cells; Molecular Mimicry; Molecular Structure; Quercetin; Selenium; Structure-Activity Relationship