2. Academic Validation
  3. Synthesis, characterization and carbonic anhydrase I and II inhibitory evaluation of new sulfonamide derivatives bearing dithiocarbamate

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

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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