Lithocholic Acid’s Ionic Compounds as Promising Antitumor Agents: Synthesis and Evaluation of the Production of Reactive Oxygen Species (ROS) in Mitochondria

The development of a methodology for the synthesis of new compounds with antitumor activity represents a significant and priority task within the field of medicinal chemistry. As a continuation of our research group's earlier studies on the antitumor activity of ionic derivatives of natural compounds, we have synthesized a series of previously undescribed pyrazole ionic compounds through a series of transformations of lithocholic acid methyl ester. To investigate the biological activity of the newly synthesized lithocholic acid derivatives, a series of modern flow cytometry techniques were employed to assess their cytotoxic activity, effects on the cell cycle, and induction of apoptosis. This included the analysis of alterations in the mitochondrial potential, accumulation of ROS ions in mitochondria, and loss of cytochrome c. These compounds demonstrate promising antitumor activity through their effects on mitochondrial oxidation and phosphorylation processes. These compounds, which we have designated as "soft dissociators", exhibit enhanced biopharmacological properties relative to the original lithocholic acid molecule.