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<p>This study employs in silico and in vitro methodologies to identify novel inhibitors for human carbonic anhydrase I and II. Schiff bases were synthesized, incorporating a pyrazole ring and a sulphonamide group. The structural characterization of the synthesized compounds <b>(3A-3F)</b> was achieved through common spectroscopic techniques. Subsequently, molecular docking studies were conducted for these compounds against Human carbonic anhydrase I (PDB ID: 1azm) and Human carbonic anhydrase II (PDB ID: 3hs4) using AutoDock Vina 1.2.3 software. The docking results revealed higher binding affinities for all compounds compared to the standard acetazolamide. Notably, compound <b>3F</b> exhibited the highest binding affinity with both proteins, leading to its selection for molecular dynamic simulation. Molecular dynamic (MD) simulations were performed to assess the dynamic behavior, stability of the protein–ligand complex, and binding affinity of compound <b>3F</b>. The results of these simulations identified compound <b>3F</b> as a promising inhibitor of hCA (I) All Schiff bases <b>(3A-3F)</b> were found to comply with Lipinski’s rule of five, indicating excellent physiochemical and pharmacokinetic properties suitable for in vivo bioavailability, as predicted by the SwissADME web tool. These synthesized novel compounds were investigated as inhibitors of the human carbonic anhydrase I and (II) The compounds exhibited moderate to potent inhibition, with Ki values ranging from 902.1 to 4832 nM for hCA I and 65.9 to 346.8 nM for hCA II. Among them, compound <b>3F</b> (3-Br) showed the most favorable activity against hCA I (Ki = 902.1 nM), whereas compound <b>3D</b> (4-Cl) displayed the strongest inhibition of hCA II (Ki  = 65.9 nM). The findings suggest that pyrazole-containing Schiff base derivatives, particularly compound <b>3D</b> and <b>3F</b>, hold potential as inhibitors of human carbonic anhydrase I and II.</p>

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Novel pyrazole-based Schiff base with carbonic anhydrase inhibitory activity: synthesis, characterization, enzyme inhibition and in silico studies

  • 期刊论文

  • 发表日期：

    2026年1月9日

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  • Viswaskumar Panchal,
  • Zakirhusen Gadhawala,
  • Arun Malaviya,
  • Simone Giovannuzzi,
  • Claudiu T. Supuran

摘要

This study employs in silico and in vitro methodologies to identify novel inhibitors for human carbonic anhydrase I and II. Schiff bases were synthesized, incorporating a pyrazole ring and a sulphonamide group. The structural characterization of the synthesized compounds (3A-3F) was achieved through common spectroscopic techniques. Subsequently, molecular docking studies were conducted for these compounds against Human carbonic anhydrase I (PDB ID: 1azm) and Human carbonic anhydrase II (PDB ID: 3hs4) using AutoDock Vina 1.2.3 software. The docking results revealed higher binding affinities for all compounds compared to the standard acetazolamide. Notably, compound 3F exhibited the highest binding affinity with both proteins, leading to its selection for molecular dynamic simulation. Molecular dynamic (MD) simulations were performed to assess the dynamic behavior, stability of the protein–ligand complex, and binding affinity of compound 3F. The results of these simulations identified compound 3F as a promising inhibitor of hCA (I) All Schiff bases (3A-3F) were found to comply with Lipinski’s rule of five, indicating excellent physiochemical and pharmacokinetic properties suitable for in vivo bioavailability, as predicted by the SwissADME web tool. These synthesized novel compounds were investigated as inhibitors of the human carbonic anhydrase I and (II) The compounds exhibited moderate to potent inhibition, with Ki values ranging from 902.1 to 4832 nM for hCA I and 65.9 to 346.8 nM for hCA II. Among them, compound 3F (3-Br) showed the most favorable activity against hCA I (Ki = 902.1 nM), whereas compound 3D (4-Cl) displayed the strongest inhibition of hCA II (Ki  = 65.9 nM). The findings suggest that pyrazole-containing Schiff base derivatives, particularly compound 3D and 3F, hold potential as inhibitors of human carbonic anhydrase I and II.