Pharmacochemical Modeling and Evaluation of Drug Molecules Used in the Treatment of Chronic Kidney Disease

Ferroptosis leads to oxidative damage and cell death. It has recently gained attention for its role in various diseases, including kidney disease. The kidneys, being highly vascularized and metabolically active organs, are susceptible to oxidative stress and iron accumulation, both of which are central to ferroptosis. Studies have shown that ferroptosis plays a significant role in drug-induced nephrotoxicity (e.g., cisplatin-induced kidney injury).

The accumulation of reactive oxygen species (ROS) in kidney cells can exacerbate the damage.

By inhibiting ferroptosis, researchers aim to slow the progression of CKD and minimize kidney fibrosis and tissue scarring. Modulating ferroptosis pathways using inhibitors could potentially provide therapeutic benefits in CKD treatment. Targeting ferroptosis may offer a promising strategy for treating conditions such as AKI, CKD, diabetic nephropathy, and polycystic kidney disease.

In this paper, iron chelators that reduce iron levels in cells were modeled and analyzed to help mitigate the risk of ferroptosis.

We also modeled a 3-phenylglutaric acid derivative and other inhibitors and investigated their pharmacochemical efficacy in the treatment of chronic kidney diseases. We assessed the thermodynamic, spectroscopic, and stereochemical properties of several inhibitors and derivatives. We used molecular editing programs to model, optimize, and compare the resulting outcomes from the test for the derivatives.