Details

Autor(en) / Beteiligte

• Bouchmaa, Najat
• Ben Mrid, Reda
• Boukharsa, Youness
• Nhiri, Mohamed
• Ait Mouse, Hassan
• Taoufik, Jamal
• Ansar, M'hammed
• Zyad, Abdelmajid

Titel

Cytotoxicity of new pyridazin‐3(2H)‐one derivatives orchestrating oxidative stress in human triple‐negative breast cancer (MDA‐MB‐468)

Ist Teil von

• Archiv der Pharmazie (Weinheim), 2018-12, Vol.351 (12), p.e1800128-n/a

Ort / Verlag

Germany: Wiley Subscription Services, Inc

Erscheinungsjahr

2018

Quelle

Wiley Online Library All Journals

Beschreibungen/Notizen

• 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, H2O2 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 H2O2 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. The antitumor effects of new pyridazin‐3(2H)‐one derivatives on the human triple‐negative breast cancer (TNBC) cell line MDA‐MB‐468 were studied. Compounds 6f and 7h were highly active (IC50 = 3.12 and 4.9 μM, respectively). Cells exposed to 6f showed significant increases in H2O2 and lipid peroxidation levels and decreased activities of glutathione reductase and thioredoxin reductase. The cytotoxicity of 6f may improve the therapeutic efficacy of the current treatment for TNBC.