Discovery of potent carbonic anhydrase, acetylcholinesterase, and butyrylcholinesterase enzymes inhibitors: The new amides and thiazolidine-4-ones synthesized on an acetophenone base

J Biochem Mol Toxicol. 2017 Sep;31(9). doi: 10.1002/jbt.21931. Epub 2017 May 22.

Abstract

Compounds containing nitrogen and sulfur atoms can be widely used in various fields, including industry, medicine, biotechnology, and chemical technology. Among them, amides of acids and heterocyclic compounds have an important place. These amides and thiazolidine-4-ones showed good inhibitory action against butyrylcholinesterase (BChE), acetylcholinesterase (AChE), and human carbonic anhydrase isoforms. AChE exists at high concentrations in the brain and red blood cells. BChE is an important enzyme that is plentiful in the liver, and it is released into the blood in a soluble form. They were demonstrated to have effective inhibition profiles with Ki values of 23.76-102.75 nM against hCA I, 58.92-136.64 nM against hCA II, 1.40-12.86 nM against AChE, and 9.82-52.77 nM against BChE. On the other hand, acetazolamide showed Ki value of 482.63 ± 56.20 nM against hCA I, and 1019.60 ± 163.70 nM against hCA II. Additionally, Tacrine inhibited AChE and BChE, showing Ki values of 397.03 ± 31.66 and 210.21 ± 15.98 nM, respectively.

Keywords: acetophenone; acetylcholinesterase; butyrylcholinesterase; carbonic anhydrase; enzyme inhibition.

MeSH terms

  • Acetophenones / chemistry*
  • Acetylcholinesterase* / chemistry
  • Butyrylcholinesterase / chemistry*
  • Carbonic Anhydrase I* / antagonists & inhibitors
  • Carbonic Anhydrase I* / chemistry
  • Carbonic Anhydrase II* / antagonists & inhibitors
  • Carbonic Anhydrase II* / chemistry
  • Carbonic Anhydrase Inhibitors* / chemical synthesis
  • Carbonic Anhydrase Inhibitors* / chemistry
  • Cholinesterase Inhibitors* / chemical synthesis
  • Cholinesterase Inhibitors* / chemistry
  • GPI-Linked Proteins / antagonists & inhibitors
  • GPI-Linked Proteins / chemistry
  • Humans
  • Thiazolidines* / chemical synthesis
  • Thiazolidines* / chemistry

Substances

  • Acetophenones
  • Carbonic Anhydrase Inhibitors
  • Cholinesterase Inhibitors
  • GPI-Linked Proteins
  • Thiazolidines
  • ACHE protein, human
  • Acetylcholinesterase
  • Butyrylcholinesterase
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II
  • acetophenone