Synthesis and In Silico Study of New Acetazolamide Derivatives Incorporating a 1,2,4-Triazole Moiety as Potential Carbonic Anhydrase Inhibitors and Anti-cancer Agents
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Abstract
A significant number of 1,2,4-triazole derivatives are known to possess numerous pharmacological properties. The present study aims to synthesize new acetazolamide derivatives with 1,2,4-triazole moiety and investigate their carbonic anhydrase inhibitory and anticancer activities in silico. Three acetazolamide derivatives having a 1,2,4-triazole moiety were synthesized from the reaction between acetazolamide and hydrazine monohydrate as starting materials. The interaction of the synthesized ligands with carbonic anhydrase XII (CAXII) enzyme (PDB code: 4QJW) a putative biomarker for solid tumors was investigated in silico via molecular docking simulation. The binding affinities of docked ligands with the target protein CAXII were reported in terms of S score and Root Mean Square Deviation (RMSD), which were calculated using the Molecular Operating Environment (MOE) software 2015 program. The docking results revealed a better binding affinity of the three test ligands (Sa, Sb, and Sc) for the target protein CAXII than the positive control ligand, acetazolamide. Of the three compounds, compound Sc showed the highest binding affinity with an S score of -7.0168. These observations suggest that the newly synthesized acetazolamide derivatives particularly compound Sc hold promise as carbonic anhydrase inhibitors, and anticancer agents targeting the CAXII enzyme.
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