Theoretical insights into the radical scavenging activity of glipizide: DFT and molecular docking studies

Glipizide is an N-sulfonylurea compound used in the treatment of hyperglycemia in patients with type 2 diabetes mellitus. In the present study, DFT-based computational methods and molecular docking studies have been performed to systematically evaluate the radical scavenger behavior of the title molecule. Structural characteristics such as molecular descriptors, frontier molecular orbitals, molecular potential mapping, and Mulliken charge population have been investigated. Thermodynamic parameters like proton affinity (PA), ionization potential (IP), bond dissociation energy (BDE), electron transfer enthalpy (ETE), and proton dissociation enthalpy (PDE) related to three antiradical mechanisms namely hydrogen atom transfer (HAT), sequential electron transfer proton transfer (SETPT) and sequential proton loss electron transfer (SPLET) have been studied. Also, molecular docking studies have been carried out to have a theoretical understanding of the molecular mechanism and for the elucidation of binding mode/modes of a compound targeted through non-covalent interactions. The obtained results are of great significance in better understanding the reaction mechanism of the title molecule and opens a new perspective for the design of potent antioxidant agents.