ADME and In Silico Profiling of Conjugated Schiff Bases to Assess Their Potential as a Human Carbonic Anhydrase II IX XII Inhibitor

Abstract

The present study investigates the ADME properties and in silico inhibitory potential of a series of conjugated Schiff bases (L1–L11) against human carbonic anhydrase isoforms II, IX, and XII, using acetazolamide, SLC-0111 (PubChem CID: 49836916), and U-104 (PubChem CID: 9813825) as reference drugs. Molecular docking using CB-Dock and AutoDock Vina revealed that ligand L5 exhibited the strongest binding affinities (–8.3, –9.0, and –9.8 kcal/mol, respectively), outperforming the reference inhibitors. ADME profiling using SwissADME indicated that all ligands complied with Lipinski's Rule of Five, with molecular weights below 500 Da, moderate LogP values, and high gastrointestinal absorption. The synthetic accessibility scores (2.32–3.34) suggested ease of laboratory synthesis. Overall, these results highlight ligand L5 as a promising human carbonic anhydrase inhibitor with favorable pharmacokinetic properties, warranting further in vitro and in vivo evaluation, particularly for isoform-specific inhibition and therapeutic potential.