Examination of Triazolinedione-Derived Dihydropyrrole Hybrid Compounds: ER Stress-Related Apoptosis in Breast Cancer Cells, Molecular Docking, and ADMET Analysis.

backgroundIn many types of cancer, uncontrolled growth and proliferation of cells occur due to abnormalities in their genes, mutations of pro-apoptotic proteins, or upregulation of anti-apoptotic proteins. Triazolinedione and pyrrole derivatives are compounds with anti-microbial, anti-fungal, anti-inflammatory, and anti-cancer activities. Pyrrole and its derivatives are critical heterocycle compounds that are significant in anticancer studies and highly preferred in research.

objectiveThis study aimed to investigate the effects of dihydropyrrole derivatives substituted with triazolinedione on the MCF-7 (breast cancer) cell line's apoptosis, ER stress, and heat shock genes.

methodsThe mRNA levels of apoptosis, ER stress, and heat shock proteins were assessed by qRT-PCR method in the MCF-7 cell line. The investigation of ADMET features, crucial pharmacokinetic indices for the potential candidacy of compounds as drugs, has been meticulously designed.

resultsIt was determined that the compounds caused cell death by modulating apoptotic (compound IV), ER stress, and heat shock proteins (compounds XI and XVI) through up- and downregulation. Our findings have pointed to the effects of triazolinedione-substituted dihydropyrrole derivatives, exhibiting antitumor activity on apoptosis, ER stress, and heat shock genes in the MCF- 7 cell line.

conclusionThe compounds investigated in this study have been found to be promising for anticancer research.