Molecular Docking Of New Acetaminophen Derivatives As Inhibitors Of Carbonic Anhydrase Enzyme with A Computational Evaluation Of Their Pharmacokinetic And Drug-Likeness Properties

Abstract

This study explores the design and computational evaluation of novel acetaminophen derivatives as potential inhibitors of carbonic anhydrase II (CA II), an enzyme implicated in various physiological and pathological processes, including glaucoma, epilepsy, and cancer. Given the limitations and side effects associated with traditional sulfonamide-based CA inhibitors, there is a pressing need for more selective and safer alternatives. Utilizing molecular docking techniques, the binding affinities and interaction modes of these derivatives within the CA II active site were assessed, with compounds A and B exhibiting promising binding energies (-6.67 and -6.47 kcal/mol, respectively) and favorable interactions with key residues such as Zn262, Asn67, and Trp5. Complementary ADMET profiling via SwissADME predicted satisfactory pharmacokinetic properties, including solubility, permeability, and drug-likeness, aligning with Lipinski’s rule. The integration of docking scores with pharmacokinetic predictions underscores the potential of these derivatives as lead candidates for further experimental validation. This computational framework highlights the feasibility of repurposing acetaminophen scaffolds for CA II inhibition, offering a strategic pathway toward the development of selective, efficacious, and safer CA inhibitors for therapeutic applications. The findings lay the groundwork for subsequent synthesis and in vitro testing, aiming to contribute to the advancement of targeted treatments with minimized adverse effects.