Abstract
As breast cancer remains a significant challenge for the current medical field, molecules with a 4-thiazolidinone scaffold can become promising candidates for addressing the increasing threat of cancer. This study aims to develop and evaluate the novel 4-thiazolidinone derivatives with anticancer potential. New compounds were synthesized through two different pathways, one as a two-step process and the other as a one-pot method. The second approach fits the requirements of cost-effective methodologies and allows for the reduction of synthetic steps, reagents, and reaction time. The obtained data from in vitro research showed a potent cytotoxic activity of the novel structures in micromolar concentrations against MCF-7 breast cancer cells. Further investigations into their anticancer activity revealed that the tested compounds induced apoptosis through intrinsic and extrinsic pathways, which was evidenced by their capability to reduce the mitochondrial membrane potential and induce the activation of caspases 7, 8, 9, and 10. A more detailed analysis uncovered that one of the novel compounds can affect the expression of key apoptotic proteins, tumor protein P53 (p53), cytochrome C, and Bax in treated cells. Additionally, these compounds displayed an enhanced generation of reactive oxygen species (ROS) in MCF-7 cells, which suggests that ROS-mediated mechanisms can take part in the anticancer potential of the synthesized compounds.