Potential antitumour and pro-oxidative effects of (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4-hydroxyphenyl) acrylate (QNACR).

Abstract

CONTEXT:

Characterization of the pro-oxidant activity of QNACR.

OBJECTIVES:

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.

• Authors: Juan R Rodrigues, Rosa Ferrer, Neira Gamboa, Jaime Charris, Fernando Antunes
• Journal: Journal of enzyme inhibition and medicinal chemistry (J Enzyme Inhib Med Chem) Vol. 28 Issue 6 Pg. 1300-6 (Dec 2013) ISSN: 1475-6374 [Electronic] England
• PMID: 23137315 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• (E)-methyl 2-(7-chloroquinolin-4-ylthio)-3-(4-hydroxyphenyl)acrylate
• Acrylates
• Antineoplastic Agents
• Antioxidants
• Quinolines
• Reactive Oxygen Species
• Thiobarbituric Acid Reactive Substances

Topics

• Acrylates (chemical synthesis, chemistry, pharmacology)
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Antioxidants (chemical synthesis, chemistry, pharmacology)
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Dose-Response Relationship, Drug
• Drug Screening Assays, Antitumor
• Humans
• Lipid Peroxidation (drug effects)
• MCF-7 Cells
• Molecular Structure
• Oxidation-Reduction
• Oxidative Stress (drug effects)
• Quinolines (chemical synthesis, chemistry, pharmacology)
• Reactive Oxygen Species (metabolism)
• Structure-Activity Relationship
• Thiobarbituric Acid Reactive Substances (metabolism)
• Tumor Cells, Cultured