Synthesis of new cyclic thioureas and evaluation of their metal-chelating activity, acetylcholinesterase, butyrylcholinesterase, and carbonic anhydrase inhibition profiles

J Biochem Mol Toxicol. 2017 Jul;31(7). doi: 10.1002/jbt.21897. Epub 2017 Jan 24.

Abstract

In the presence of trifluoracetic acid (TFAA), an efficient method for the synthesis of tetra(hexa)hydropyrimidinethione-carboxylates has been used on the basis of three-component condensation of thiourea with its different aldehydes and β-diketones. Some novel cyclic thioureas were synthesized, and their hCA I, hCA II, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) inhibitors and metal-chelating properties were evaluated. Ki values of novel synthesized compounds for AChE and BChE are in the range of 51.84-135.96 and 143.96-274.55 nM, respectively. Also, HCA I and II were effectively inhibited by these novel compounds, with Ki values in the range of 404.16-745.13 nM for hCA I and of 434.20-689.57 nM for hCA II, respectively. Additionally, acetazolamide (AZA), clinically used as a CA inhibitor, with a Ki value of 883.68 ± 121.27 nM in hCA I and 1008.66 ± 144.70 nM in hCA II. Also, tacrine inhibited AChE and BChE showed Ki values of 314.63 ± 31.66 and 373.57 ± 75.07 nM, respectively.

Keywords: acetylcholinesterase; butyrylcholinesterase; carbonic anhydrase; metal chelating; thiourea.

MeSH terms

  • Acetylcholinesterase / chemistry*
  • Butyrylcholinesterase / chemistry*
  • Carbonic Anhydrase Inhibitors* / chemical synthesis
  • Carbonic Anhydrase Inhibitors* / chemistry
  • Carbonic Anhydrases / chemistry*
  • Cholinesterase Inhibitors* / chemical synthesis
  • Cholinesterase Inhibitors* / chemistry
  • Thiourea* / chemical synthesis
  • Thiourea* / chemistry

Substances

  • Carbonic Anhydrase Inhibitors
  • Cholinesterase Inhibitors
  • Acetylcholinesterase
  • Butyrylcholinesterase
  • Carbonic Anhydrases
  • Thiourea