In vitro cytotoxic, antioxidant, hemolytic and cytoprotective potential of promising ethacrynic acid derivatives

The present study aims to screen some pharmacological activities of three promising ethacrynic acid (EA) derivatives (P3, P4, and P5) containing a piperazine moiety. The EA derivatives were tested against MDA-MB-468 cancer cell line as a model for the triple-negative breast cancer and MCF7 cancer cell line as a model subtype of luminal breast cancer using the methyl tetrazolium test (MTT). Additionally, the modulation of the glutathione and thioredoxin enzymatic systems, as well as the antioxidant and cytoprotective potential of each compound, were investigated. Moreover, initial in vitro safety screening was conducted using human blood cells. As a result, EA derivatives showed clear dose-dependent antiproliferative activity in the micromolar range (between 1.13 and 2.51 mu M), with high selectivity to cancer cells by orchestrating oxidative stress. Derivative P3 has the most promising potential for further preclinical investigation, owing to its safety profile and significant cytoprotective and antitumor properties.