Article
Potential antitumor and pro-oxidative effects of (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4-hydroxyphenil)acrylate (QNACR)
Autor
Rodrigues, Juan
Ferrer, Rosa
Gamboa, Neira
Charris, Jaime
Antunes, Fernando
Institución
Resumen
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.
Conclusion: QNACR led to remarkable modifications in the oxidative status of tumour cells, proposing this compound
as potential alternative for antitumour therapy. 1Laboratory of Biochemistry of Oxidants and Antioxidants, Centre and Department of Chemistry and Biochemistry,
School of Sciences, University of Lisbon, Lisbon, Portugal and 2Laboratory of Organic Synthesis and Biochemistry,
School of Pharmacy, Central University of Venezuela, Los Chaguaramos, Caracas, Venezuela