Investigation of the effect of isoxazole derivatives on glutathione-dependent enzymes associated with cancer

Globally, cancer is currently the second-most common cause of death. As such, it is a crucial problem that affects society's well-being all around the world. Chemotherapy is the most commonly used treatment for cancer. It is a technique that uses drugs to kill cancerous cells or the cancerous organism itself. Chemotherapy has been used to treat metastatic cancer for the past 50 years, with varying degrees of effectiveness. One of the main problems with many chemotherapeutic drugs is that they might damage healthy cells and organs. These drugs frequently have a low therapeutic index, a restricted ability to selectively target cancerous cells, and a high propensity to develop drug resistance after extended use. Furthermore, a rise in the expression of glutathione reductase (GR; EC 1.8.1.7) and glutathione S-transferase (GST; EC 2.5.1.18) can be seen with time. Extensive study on proteins and their functions in the development of cancer cells has been conducted in recent years. Glutathione-S-transferases (GSTs) are a superfamily of enzymes that play a critical role in the detoxification of cells by protecting them against reactive electrophiles such as chemotherapeutic drugs and reactive oxygen species. Glutathione reductase (GR), on the other hand, is an essential antioxidant enzyme that supports cellular protection against oxidative stress. In addition to its antioxidant role, GR has become a target for the synthesis of antimalarial and anticancer medications. In the current investigation, affinity chromatography was used to purificate the GST and GR enzymes from human erythrocytes. Through the calculation of IC50 and KI values for these derivatives, the effects of isoxazole derivatives on these purified enzymes were examined, with an emphasis on identifying the forms of inhibition.