Theoretical study on molecular stability, reactivity, and drug potential of cirsilineol from DFT and molecular docking methods

Abstract

Molecular stability, chemical reactive sites, and global reactivity descriptors of cirsilineol have been investigated by using computational and molecular docking approaches. The density functional theory (DFT) was employed with the functional B3LYP/6–311++G(d,p). The lowest energy structure of cirsilineol was investigated, with an energy of -767,080.1261 kcal/mol. The hydrogen bonding investigation based on the QTAIM study showed that H31…O5 has the strongest interaction. RDG isosurface has also provided insights into intra-molecular hydrogen bonding and other interactions. The high ELF value for hydrogen suggested that electrons were more localized in it. The lone pair interaction LP(2)O6 → π*(C18-C20) with a higher stabilization energy of 73.08 kcal/mol is crucial to the stabilization of the molecule, and the oxygens and hydrogens with methyl groups function as nucleophilic and electrophilic sites in the molecule. The chemical reactivity and hardness of the molecule in terms of the HOMO-LUMO energy gap (ΔEL-H) have been carried. Moreover, molecular docking of the title molecule with the enzyme Aldose reductase has been performed to check the binding interaction as well as the reactive sites of the molecule.

Keywords

• Cirsilineol
• Natural bond orbital
• Reduced density gradient
• Global reactivity
• QTAIM
• Aldose reductase