Abstract
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 cytoxic when compared with their oxo and thioanalogues, 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.
Original language | English |
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Pages (from-to) | 4250-4265 |
Number of pages | 16 |
Journal | Journal Of Medicinal Chemistry |
Volume | 58 |
Issue number | 10 |
DOIs | |
Publication status | Published - 28 May 2015 |
Keywords
- MAMMALIAN THIOREDOXIN REDUCTASE
- OVARIAN-CARCINOMA CELLS
- ORGANOSELENIUM COMPOUNDS
- ANTICANCER AGENTS
- IN-VIVO
- MITOCHONDRIAL THIOREDOXIN
- DISSOCIATION ENTHALPY
- CISPLATIN RESISTANCE
- ANTIOXIDANT ACTIVITY
- NEUTRON-DIFFRACTION