title: Potential antitumour and pro-oxidative effects of (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4-hydroxyphenyl) acrylate (QNACR).
abstract: BACKGROUND
  Characterization of the pro-oxidant activity of QNACR.
  
  
  OBJECTIVE
  Reactive oxygen species (ROS) induce cellular damage and represent unique opportunities to kill malignant cells. In this study, we synthesized and evaluated the new compound, (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4-hydroxyphenyl) acrylate (QNACR) as potential pro-oxidative agent against breast cancer.
  
  
  METHODS
  Oxidative stress biomarkers such as ROS, thiobarbuturic acid reactive species (TBARs) and different antioxidant enzyme activities were determined in cell lysates.
  
  
  RESULTS
  QNACR showed cytotoxic and more selective effects to tumour MCF7 cells (IC50 < 25 µM) compared to antitumour controls, inducing ROS and TBARs parallel to inhibitions of catalase (CAT), glucose-6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH). Longer exposures to QNACR triggered adaptive effects increasing the overall activities of CAT, glutathione reductase, G6PDH and 6PGDH, but eventually the adaptation changes faded and cells died.
  
  
  CONCLUSIONS
  QNACR led to remarkable modifications in the oxidative status of tumour cells, proposing this compound as potential alternative for antitumour therapy.
authors.affiliation: Laboratory of Biochemistry of Oxidants and Antioxidants, Centre and Department of Chemistry and Biochemistry, School of Sciences, University of Lisbon , Lisbon , Portugal.
authors.forename: Juan R
authors.initials: JR
authors.lastname: Rodrigues
authors.forename: Rosa
authors.initials: R
authors.lastname: Ferrer
authors.forename: Neira
authors.initials: N
authors.lastname: Gamboa
authors.forename: Jaime
authors.initials: J
authors.lastname: Charris
authors.forename: Fernando
authors.initials: F
authors.lastname: Antunes
mesh_terms: D000179:Acrylates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D061986:MCF-7 Cells; D015394:Molecular Structure; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013329:Structure-Activity Relationship; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: C000589136:(E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4-hydroxyphenyl)acrylate; D000179:Acrylates; D000970:Antineoplastic Agents; D000975:Antioxidants; D011804:Quinolines; D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances