Selenium-containing chrysin and quercetin derivatives: attractive scaffolds for cancer therapy

J Med Chem. 2015 May 28;58(10):4250-65. doi: 10.1021/acs.jmedchem.5b00230. Epub 2015 May 7.

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 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor / drug effects
  • Cell Survival / drug effects
  • Chemistry Techniques, Synthetic
  • Cisplatin / pharmacology
  • Drug Resistance, Multiple / drug effects
  • Drug Resistance, Neoplasm / drug effects
  • Drug Screening Assays, Antitumor
  • Flavonoids / chemistry*
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • MCF-7 Cells / drug effects
  • Magnetic Resonance Spectroscopy
  • Molecular Mimicry
  • Molecular Structure
  • Quercetin / chemistry*
  • Selenium / chemistry
  • Selenium / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Flavonoids
  • Free Radical Scavengers
  • chrysin
  • Quercetin
  • Selenium
  • Cisplatin