Selenium-Containing Chrysin and Quercetin Derivatives: Attractive Scaffolds for Cancer Therapy

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.