In silico exploration of selected coumarin derivatives as potential antioxidant: Insights from DFT, NBO, Hirshfeld surface, ADMET profiling, Molecular docking and Dynamics simulations

Abstract

Coumarin derivatives have been explored as highly promising antioxidants due to their significant binding mechanisms with radicals and protein residues. Herein, we have selected a few bioactive coumarin derivatives to investigate their effectiveness in complexation with alkoxy (RO•) and hydroperoxyl (HOO•) radicals as well as with carbonic anhydrase VII (CA VII) protein. To gain further insights, in silico studies viz., DFT, pharmacokinetic evaluation (ADMET) and drug-likeness assessments, etc., are useful to analyze the complex formation mechanism with radicals and protein residues. Again, Molecular Electrostatic Potential (MEP), Spin Density (SD) and Natural Bond Orbital (NBO) studies display superior binding interactions with the protein residues characterized by conventional H-bonding along with other hydrophobic interactions. Moreover, molecular docking, dynamics and physicochemical analysis reveal that all coumarin derivatives interact effectively within the internal cavity of CA VII, detailing binding affinities and specific protein residues involved.