Microwave-assisted synthesis and bioevaluation of new sulfonamides

J Enzyme Inhib Med Chem. 2017 Dec;32(1):369-374. doi: 10.1080/14756366.2016.1254207.

Abstract

In this study, 4-[5-(4-hydroxyphenyl)-3-aryl-4,5-dihydro-1H-pyrazol-1-yl]benzenesulfonamide derivatives (8-14) were synthesized for the first time by microwave irradiation and their chemical structures were confirmed by 1H NMR, 13C NMR and HRMS. Cytotoxic activities and inhibitory effects on carbonic anhydrase I and II isoenzymes of the compounds were investigated. The compounds 9 (PSE = 4.2), 12 (PSE = 4.1) and 13 (PSE = 3.9) with the highest potency selectivity expression (PSE) values in cytotoxicity experiments and the compounds 13 (Ki = 3.73 ± 0.91 nM toward hCA I) and 14 (Ki = 3.85 ± 0.57 nM toward hCA II) with the lowest Ki values in CA inhibition studies can be considered as leader compounds for further studies.

Keywords: Carbonic anhydrase; cytotoxicity; microwave; pyrazoline; sulfonamide.

MeSH terms

  • Adenylyl Cyclases / metabolism
  • Biological Assay
  • Carrier Proteins / antagonists & inhibitors*
  • Carrier Proteins / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Enzyme Inhibitors / toxicity
  • Humans
  • Microwaves*
  • Molecular Structure
  • Nerve Tissue Proteins / antagonists & inhibitors*
  • Nerve Tissue Proteins / metabolism
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / classification
  • Sulfonamides / pharmacology*
  • Sulfonamides / toxicity

Substances

  • Carrier Proteins
  • Enzyme Inhibitors
  • MAGEE1 protein, human
  • Nerve Tissue Proteins
  • Sulfonamides
  • ADCY10 protein, human
  • Adenylyl Cyclases