Synthesis, molecular docking analysis and carbonic anhydrase I-II inhibitory evaluation of new sulfonamide derivatives

Bioorg Chem. 2019 Oct:91:103153. doi: 10.1016/j.bioorg.2019.103153. Epub 2019 Jul 29.

Abstract

New sulfonamide-hydrazone derivatives (3a-3n) were synthesized to evaluate their inhibitory effects on purified human carbonic anhydrase (hCA) I and II. The inhibition profiles of the synthesized compounds on hCA I-II isoenzyme were investigated by comparing their IC50 and Ki values. Acetazolamide (5-acetamido-1,3,4-thiadiazole-2-sulfonamide, AZA) has also been used as a standard inhibitor. The compound 3e demonstrated the best hCA I inhibitory effect with a Ki value of 0.1676 ± 0.017 µM. Besides, the compound 3m showed the best hCA II inhibitory effect with a Ki value of 0.2880 ± 0.080 µM. Cytotoxicity of the compounds 3e and 3m toward NIH/3T3 mouse embryonic fibroblast cell line was observed and the compounds were found to be non-cytotoxic. Molecular docking studies were performed to investigate the interaction types between active compounds and hCA enzymes. Pharmacokinetic profiles of compounds were assessed by theoretical ADME predictions. As a result of this study a novel and potent class of CA inhibitors were identified with a good activity potential.

Keywords: ADME; Carbonic anhydrase; Cytotoxicity; Molecular docking; Sulfonamide.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetamides / chemical synthesis*
  • Acetamides / pharmacology*
  • Animals
  • Carbonic Anhydrase I / antagonists & inhibitors*
  • Carbonic Anhydrase II / antagonists & inhibitors*
  • Carbonic Anhydrase Inhibitors / chemical synthesis*
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Humans
  • Mice
  • Molecular Docking Simulation
  • Molecular Structure
  • NIH 3T3 Cells
  • Structure-Activity Relationship

Substances

  • Acetamides
  • Carbonic Anhydrase Inhibitors
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II