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

Ines L. Martins, Catarina Charneira, Valentina Gandin, Joao L. Ferreira da Silva, Goncalo C. Justino, Joao P. Telo, Abel José de Sousa Costa Vieira, Cristina Marzano, Alexandra M. M. Antunes

Research output: Contribution to journalArticle

54 Citations (Scopus)

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 languageEnglish
Pages (from-to)4250-4265
Number of pages16
JournalJournal Of Medicinal Chemistry
Volume58
Issue number10
DOIs
Publication statusPublished - 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

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