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

  • Eur J Med Chem. 2020 Jul 15;198:112392. doi: 10.1016/j.ejmech.2020.112392.
Begüm Nurpelin Sağlık  1 ,  Derya Osmaniye  2 ,  Ulviye Acar Çevik  2 ,  Serkan Levent  2 ,  Betül Kaya Çavuşoğlu  3 ,  Oya Büyükemir  4 ,  Deniz Nezir  4 ,  Abdullah Burak Karaduman  5 ,  Yusuf Özkay  2 ,  Ali Savaş Koparal  6 ,  Şükrü Beydemir  4 ,  Zafer Asım Kaplancıklı  7
Affiliations
  • 1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey; Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey. Electronic address: [email protected].
  • 2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey; Doping and Narcotic Compounds Analysis Laboratory, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
  • 3. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Zonguldak Bülent Ecevit University, 67600 Zonguldak, Turkey.
  • 4. Department of Biochemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
  • 5. Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
  • 6. Open Education Faculty, Anadolu University, 26470 Eskişehir, Turkey.
  • 7. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 26470 Eskişehir, Turkey.
PMID: 32388113 DOI: 10.1016/j.ejmech.2020.112392
Abstract

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 Ki values of 0.032 ± 0.001 μM and 0.013 ± 0.0005 μM, 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.

Keywords
Carbonic anhydrase; Cytotoxicity; Dithiocarbamate; Molecular docking; Sulfonamide.
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