Medicinal Chemistry Research

, Volume 26, Issue 10, pp 2293–2308 | Cite as

Design, synthesis, and molecular modeling of new 3(2H)-pyridazinone derivatives as acetylcholinesterase/butyrylcholinesterase inhibitors

  • Zeynep Özdemir
  • Hayriye Yılmaz
  • Suat Sarı
  • Arzu Karakurt
  • Fatma Sezer Şenol
  • Mehtap Uysal
Original Research


Inhibition of cholinesterases is an effective method to curb Alzheimer’s disease, a progressive and fatal neurological disorder. A series of 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(p-substituted benzalhidrazone) derivatives were designed, synthesized, and their inhibitory effects on acetylcholinesterase and butyrylcholinesterase were evaluated in pursuit of potent dual inhibitors. We obtained our compounds by the reaction of various substituted/nonsubstituted benzaldehydes with 6-[4-(3,4-dichlorophenyl)piperazine-1-yl]-3(2H)-pyridazinone-2-yl acetohydrazide and determined their anticholinesterase activities according to the Ellman’s method. 5f and 5i showed 75.52 and 71.72% acetylcholinesterase inhibition at 100 µg/ml, respectively. 5h and 5f, on the other hand, were the best butyrylcholinesterase inhibitors with 67.16 and 62.03% inhibition at the same concentration, respectively. 5f emerged as a potent dual cholinesterase inhibitor. Through molecular docking studies we predicted the inhibition mechanism of 5f for both enzymes in comparison with our previous derivatives, which differ in inhibition potency, and tried to get insights into the factors that affect receptor affinity in molecular level.


AChE inhibitory BChE inhibitory 3(2H)-Pyridazinone Benzalhydrazone Molecular docking 



This study was funded by the Research Foundation of İnönü University (2013/94).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

44_2017_1930_MOESM1_ESM.pdf (16.1 mb)
Supplementary Information


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Copyright information

© Springer Science+Business Media New York 2017

Authors and Affiliations

  • Zeynep Özdemir
    • 1
  • Hayriye Yılmaz
    • 2
  • Suat Sarı
    • 3
  • Arzu Karakurt
    • 1
  • Fatma Sezer Şenol
    • 4
  • Mehtap Uysal
    • 5
  1. 1.Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Inonu UniversityMalatyaTurkey
  2. 2.Kayseri Vocational School, Department of Biomedical Devices and Technologies, Erciyes UniversityKayseriTurkey
  3. 3.Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Hacettepe UniversityAnkaraTurkey
  4. 4.Faculty of Pharmacy, Department of Pharmacognosy, Gazi UniversityAnkaraTurkey
  5. 5.Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Gazi UniversityAnkaraTurkey

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