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

SAĞLIK B. N., ACAR ÇEVİK U., OSMANİYE D., LEVENT S., KAYA ÇAVUŞOĞLU B., Demir Y., ...More

BIOORGANIC CHEMISTRY, vol.91, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 91
  • Publication Date: 2019
  • Doi Number: 10.1016/j.bioorg.2019.103153
  • Journal Name: BIOORGANIC CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Index Chemicus (IC)
  • Keywords: Carbonic anhydrase, Sulfonamide, Cytotoxicity, Molecular docking, ADME, BIOLOGICAL EVALUATION, ISOZYMES I, ISOFORMS I, DRUG DESIGN, HYDRAZONE, POTENT, COMPLEXES, XII, SOLUBILITY, ANALOGS
  • Anadolu University Affiliated: Yes

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 K-i values. Acetazolamide (5-acetamido-1,3,4-thia-diazole-2-sulfonamide, AZA) has also been used as a standard inhibitor. The compound 3e demonstrated the best hCA I inhibitory effect with a K-i value of 0.1676 +/- 0.017 mu M. Besides, the compound 3m showed the best hCA II inhibitory effect with a K-i value of 0.2880 +/- 0.080 mu M. 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.