Synthesis and Inhibitor Effect Novel Alkoxymethyl Derivatives of Dihetero Cycloalkanes on Carbonic Anhydrase and Acetylcholinesterase

Chem Biodivers. 2024 Jun;21(6):e202400296. doi: 10.1002/cbdv.202400296. Epub 2024 May 3.


1,3-Diheterocycloalkanes derivatives are important starting materials in fine organic synthesis. These compounds can be widely used in various fields such as industry, medicine, biotechnology and chemical technology. The paper is focused on synthesis and study of alkoxymethyl derivatives of diheterocycloalkanes (M1-M15) and inhibition effect on carbonic anhydrase and acetylcholinesterase. The structures of compounds were confirmed by 1H and 13C NMR spectroscopy. Also, in this study alkoxymethyl derivatives of diheterocycloalkanes were assessed for their influence on various metabolic enzymes, including acetylcholinesterase (AChE) and human carbonic anhydrase isoenzymes (hCA I and hCA II). The results demonstrated that all these compounds exhibited potent inhibitory effects on all the target enzymes, surpassing the standard inhibitors, as evidenced by their IC50 and Ki values. The Ki values for the compounds concerning AChE, hCA I, and hCA II enzymes were in the ranges of 1.02±0.17-8.38±1.02, 15.30±3.15-58.14±5.17 and 24.05±3.70-312.94±27.24 nM, respectively.

Keywords: 1,3-imidazolidine; 1,3-oxazine; 1,3-oxazolidine; acetylcholinesterase; benzothiazol-2-thione; carbonic anhydrase; enzyme inhibition.

MeSH terms

  • Acetylcholinesterase* / metabolism
  • Carbonic Anhydrase I* / antagonists & inhibitors
  • Carbonic Anhydrase I* / metabolism
  • Carbonic Anhydrase II* / antagonists & inhibitors
  • Carbonic Anhydrase II* / metabolism
  • Carbonic Anhydrase Inhibitors* / chemical synthesis
  • Carbonic Anhydrase Inhibitors* / chemistry
  • Carbonic Anhydrase Inhibitors* / pharmacology
  • Cholinesterase Inhibitors* / chemical synthesis
  • Cholinesterase Inhibitors* / chemistry
  • Cholinesterase Inhibitors* / pharmacology
  • Cycloparaffins* / chemical synthesis
  • Cycloparaffins* / chemistry
  • Cycloparaffins* / pharmacology
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship


  • Acetylcholinesterase
  • Cholinesterase Inhibitors
  • Carbonic Anhydrase Inhibitors
  • Carbonic Anhydrase II
  • Carbonic Anhydrase I
  • Cycloparaffins