Synthesis, characterization and carbonic anhydrase I and II inhibitory evaluation of new sulfonamide derivatives bearing dithiocarbamate

SAĞLIK B. N., OSMANİYE D., ACAR ÇEVİK U., LEVENT S., ÇAVUŞOĞLU B. K., Buyukemir O., ...Daha Fazla

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, cilt.198, 2020 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 198
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1016/j.ejmech.2020.112392
  • Dergi Adı: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chimica, EMBASE, MEDLINE, Veterinary Science Database, Index Chemicus (IC)
  • Anahtar Kelimeler: Carbonic anhydrase, Cytotoxicity, Dithiocarbamate, Molecular docking, Sulfonamide, COMPLEXES, BINDING, DESIGN
  • Anadolu Üniversitesi Adresli: Evet

Özet

In this study, novel dithiocarbamate-sulfonamide derivatives (3a-3k) were synthesized to investigate their inhibitory activity on purified human carbonic anhydrase (hCA) I and II. The IC50 and Ki values of the compounds were calculated to compare their inhibition profiles on hCA I and II isoenzymes. Acetazolamide was used as the standard inhibitor in the enzyme inhibition assay. Compounds 3a, 3e, 3g, 3h, 3j and 3k showed notable inhibitory effects against hCA I and II. Among these compounds, compound 3h was found to be the most active derivate against both the hCA I and II enzymes with K-i values of 0.032 +/- 0.001 mM and 0.013 +/- 0.0005 mM, respectively. The cytotoxicity of compounds 3a, 3e, 3g, 3h, 3j and 3k toward NIH/3T3 (mouse embryonic fibroblast cell line) was observed and the compounds were found to be non-cytotoxic. Furthermore, molecular docking studies were performed to investigate the interaction types between compound 3h and the hCA I and II enzymes. As a result of this study a novel and potent class of CA inhibitors with good activity potential were identified. (C) 2020 Elsevier Masson SAS. All rights reserved.