4194659 - Chemosynthetic livers: Predict, prepare and prove the structure, activity and toxicity of drug metabolites - Results on polypharmacy

The Chorghade-Dolphin azamacrocyclic catalysts are highly effective due to their electronic activation and steric protection, making them fast-acting, stable, and scalable. We use these catalysts to predict metabolite structures and synthesize them on a laboratory scale through oxidation reactions. As metabolites have been linked to adverse side effects, they have been under constant scrutiny in drug R&D. Polypharmacy, common among the elderly and chronically ill, poses a significant risk of drug-drug interactions (DDIs) and adverse drug responses (ADRs). Certain pharmaceuticals can cause irreversible changes to the formation of metabolites when they interact with other drugs, leading to differences in toxicity and efficacy. We present the results of successful studies to predict and validate adaptation of oxidative metabolites from combinations of widely used medications for diabetes, hypercholesterolemia, hypertension, and cancer. Our findings unequivocally demonstrate that some of these molecules dimerize in diluted aqueous solution or that various complexes can form between disparate molecules. Our potent combination works as an "in vitro cocktail" that physicians may use to dynamically assess a patient's response (DDI, dosage amounts, and regimens) to various medications to prescribe the right combination of drugs for effectual dosages.