New aminobenzenesulfonamide-thiourea conjugates: synthesis and carbonic anhydrase inhibition and docking studies

Eur J Med Chem. 2014 May 6:78:140-50. doi: 10.1016/j.ejmech.2014.03.023. Epub 2014 Mar 12.

Abstract

A variety of 1-substituted-3-(3-aminosulfonylphenyl)thioureas (3a-k) and two new 1-aroyl-3-(4-aminosulfonylphenyl)thiourea derivatives (5a and 5b) were synthesized by reaction of 3-aminobenzenesulfonamide and 4-aminobenzenesulfonamide respectively with freshly prepared aroyl/heteroaryl isothiocyanates in dry acetonitrile. FTIR, (1)H NMR, (13)C NMR, GC-MS and elemental analyses data confirmed the assigned structures to the synthesized compounds. Further structure of compound (3g) was also confirmed by single crystal XRD analysis. The compounds were investigated as inhibitors of the bovine erythrocyte carbonic anhydrase isoform II (bCA II). The inhibition constants of these compounds against bCA II were in the range 0.011-17.1 μM. Among the evaluated compounds, 1-substituted -3-(3-aminosulfonylphenyl)thiourea derivatives 3h and 5a were the most potent inhibitors with IC50 of 0.052 and 0.011 μM, respectively. In silico docking and molecular dynamics simulation studies were performed against bCA II and human CA II enzymes to rationalize the inhibitory properties of these compounds.

Keywords: 1-Aroyl/heteroaryl-3-(3-aminosulfonylphenyl)thioureas; 3-Aminobenzenesulfonamide; Carbonic anhydrase; Molecular dynamics simulation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / metabolism*
  • Cattle
  • Dose-Response Relationship, Drug
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship
  • Sulfanilamides / chemistry
  • Sulfanilamides / pharmacology*
  • Thiourea / chemistry
  • Thiourea / pharmacology*

Substances

  • Carbonic Anhydrase Inhibitors
  • Isoenzymes
  • Sulfanilamides
  • Carbonic Anhydrases
  • Thiourea