Thermochemical, Molecular docking and ADMET studies of Aspirin metabolites

Abstract

Aspirin (Asp) is a member of nonsteroidal anti-inflammation drug and widely used as an analgesic, antipyretic, and anti-inflammation agent. In this investigation, the inherent stability, chemical reactivity, and biological properties of Aspirin and its metabolites have been studied. Density functional theory (DFT) with B3LYP/3-21g has been employed to optimize the structures. Frontier molecular orbital features (HOMO-LUMO gap, hardness, and softness), dipole moment, electrostatic potential and thermodynamic properties (electronic energy, enthalpy, Gibb's free energy) of these metabolites have been investigated. Molecular docking has been performed against prostaglandin H2 (PGH2) synthase protein 5F19 to search the binding affinity and mode(s) of all compounds. It is found that, all compounds are thermodynamically stable; most of them are chemically more reactive and show better binding affinity than the parent drug. ADMET calculations predict the improved pharmacokinetic properties of all metabolites.