Synthesis and Anticancer Activity Evaluation of New 5-((5-Nitrofuran-2-yl)allylidene)-2-thioxo-4-thiazolidinones.

Background/

Objectives

Cancer persists as a leading concern in the current medical field. As such, scientists are continuously researching new compounds with anticancer potential. In this study, we explored fifteen new 4-thiazolidinone derivatives as potential anticancer compounds. 4-Thiazolidinones are a well-established group of active structures, most commonly applied for the treatment of Parkinson's disease and diabetic neuropathy. However, they are actively researched as potential anticancer agents. A number of derivatives have qualified for Phase II and III clinical trials as antitumor agents.

Methods

MTT cytotoxicity assay was applied to identify the most active compounds. Three out of the fifteen tested structures displayed a significant inhibitory effect on the MCF-7 and MDA-MB-231 cell lines. To further investigate the influence of compounds on breast cancer cells, we analyzed their capability to induce apoptosis using flow cytometry assessment with Annexin V and propidium iodide dyes. Next, flow cytometry analysis of JC-1 dye was utilized to research their capability to affect mitochondrial membrane. Afterwards, concentrations of important proapoptotic proteins such as Bax and cytochrome C were assessed with a highly sensitive ELISA method.

Results

Further analysis with a fluorescent microscope displayed that novel compounds significantly increase the generation of reactive oxygen species.

Conclusions

The results represented in this article displayed that the most active compounds positively affected the activation of the intrinsic apoptotic pathway in the tested breast cancer cells.