• Maria Hristova Medical University - Sofia, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Sofia
  • Mariyana Atanasova Medical University - Sofia, Faculty of Pharmacy, Department of Chemistry, Sofia
  • Iva Valkova Medical University - Sofia, Faculty of Pharmacy, Department of Chemistry, Sofia
  • Lilya Andonova Medical University - Sofia, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Sofia
  • Irini Doytchinova Medical University - Sofia, Faculty of Pharmacy, Department of Chemistry, Sofia
  • Alexander Zlatkov Medical University - Sofia, Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Sofia
Keywords: acetylcholinesterase, molecular docking, AChE inhibitors


Acetylcholinesterase (AChE) is a good target in the design of new drugs for the treatment of Alzheimer’s disease. The currently known drugs -donepezil, galantamine and rivastignime- act as moderate AChE inhibitors. In the present study, we docked a newly synthesized arylpiperazine derivative 1-(3-(4-benzylpiperazin-1-yl)propyl)-3,7-dimethyl-1H-purine-2,6(3H,7H)-dione (LA1) into rhAChE and identified its binding mode. The docking pose of the studied LA1 molecule depends of the protonated state of the nitrogen atom of the piperazine moiety where in the best scored poses, the xanthine moiety of LA1 is bound into the catalytic active site (CAS) of AChE, while the arylpiperazine fragment is placed into the peripheral binding site (PAS). The Ellman’s test confirmed the compound binding. LA1 has good permeability through the GIT and BBB assessed by PAMPA. LA1 is a prospective lead for AChE inhibition.


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