Probing the interaction mechanisms of organophosphate pesticide Profenofos with Diabetes associated proteins: Molecular Docking and ADME-Toxicity studies

This study examines at the molecular interactions of Profenofos with essential human proteins, as well as quantum chemical analysis to optimize its structure and analyze frontier molecular orbitals. The predicted HOMO and LUMO energies were -6.7558 eV and -1.0841 eV, respectively, using DFT-based optimization at the B3LYP/LANL2DZ level. This has resulted in a band gap of 5.6717 eV. Profenofos's persistence in biological and environmental systems is supported by the large energy gap, which shows strong chemical stability and low reactivity. Sirtuin-3 showed the highest binding energy of -6.1 kcal/mol among the protein targets evaluated by molecular docking. This was caused by strong hydrogen bonding, π-alkyl, and electrostatic interactions that promote stable and selective complex formation. Lecithin-Cholesterol Acyltransferase (LCAT), Paraoxonase-1, and Carnitine Palmitoyltransferase-1 (CPT1) showed moderate affinities of -5.4 kcal/mol, -5.8 kcal/mol, and -5.7 kcal/mol, which were mostly maintained by non-polar interactions. With no hydrogen bonding and the weakest interaction (-4.6 kcal/mol), Toll-like Receptor 4 (TLR4) demonstrated poor binding selectivity. High plasma protein binding, low water solubility, and effective intestinal absorption were found by ADMET profiling, indicating restricted free circulation but prolonged retention. Profenofos presents metabolic issues because of cytochrome P450 inhibition and possible endocrine disruption, despite not being mutagenic or cardiotoxic. Furthermore, there are serious threats to ecological systems and human health due to its bioaccumulative nature and environmental toxicity.