1. Cytotoxicity of new pyridazin-3(2H)-one derivatives orchestrating oxidative stress in human triple-negative breast cancer (MDA-MB-468).
- Author
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Bouchmaa N, Ben Mrid R, Boukharsa Y, Nhiri M, Ait Mouse H, Taoufik J, Ansar M, and Zyad A
- Subjects
- Antineoplastic Agents chemical synthesis, Antineoplastic Agents chemistry, Cell Line, Tumor, Cell Survival drug effects, Female, Humans, Inhibitory Concentration 50, Leukocytes, Mononuclear drug effects, Molecular Structure, Pyridazines chemical synthesis, Pyridazines chemistry, Reactive Oxygen Species metabolism, Triple Negative Breast Neoplasms pathology, Antineoplastic Agents pharmacology, Oxidative Stress drug effects, Pyridazines pharmacology, Triple Negative Breast Neoplasms metabolism
- Abstract
Triple-negative breast cancer (TNBC) is a complex and aggressive subtype of breast cancer characterized by high morbidity and mortality. In the absence of targeted therapy, only chemotherapy is available in this case of cancer. The current study investigated the antitumor effect of new pyridazin-3(2H)-one derivatives on the human TNBC cell line, MD-MB-468. The in vitro cytotoxic activities were investigated using the tetrazolium-based MTT assay. Lipid peroxidation, H
2 O2 content, and the specific activities of antioxidant enzymes were also determined. Two molecules, 6f and 7h, were found to be selectively highly active against tumor cells with IC50 values of 3.12 and 4.9 µM, respectively. Furthermore, cells exposed to 6f showed a significant increase in H2 O2 and lipid peroxidation levels, accompanied by a decrease in the enzyme activities of glutathione reductase (GR) and thioredoxin reductase (TrxR). The cytotoxicity of the compound 6f may improve the therapeutic efficacy of the current treatment for TNBC via the inhibition of GR and TrxR activities., (© 2018 Deutsche Pharmazeutische Gesellschaft.)- Published
- 2018
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