A Series of New Hydrazone Derivatives: Synthesis, Molecular Docking and Anticholinesterase Activity Studies

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Author(s): İrem Bozbey, Zeynep Özdemir*, Harun Uslu, Azime Berna Özçelik, Fatma Sezer Şenol, İlkay Orhan Erdoğan, Mehtap Uysal.

Journal Name: Mini-Reviews in Medicinal Chemistry

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Background: Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are known serine hydrolase enzymes responsible for the hydrolysis of acetylcholine (ACh), which is a significant neurotransmitter for regulation of cognition in animals. Inhibition of cholinesterases is an effective method to curb Alzheimer’s disease, a progressive and fatal neurological disorder. Docking studies were performed for the compounds F18 and F111 also interaction modes using AChE and BChE enzymes active sites were determined.

Objective: In this study, 30 new hydrazone derivatives were synthesized. Then, we evaluated their anticholinesterase activity of compounds. We also tried to get insights into binding interactions of the synthesized compounds in the active site of both enzymes by using molecular docking approach.

Method: The compounds were synthesized by the reaction of various substituted/nonsubstituted benzaldehydes with 6-(substitute/nonsubstituephenyl)-3(2H)-pyridazinone-2-yl propiyohydrazide. Anticholinesterase activity of the compounds were determined according to the Ellman’s method. Molecular docking studies were done by using the ADT package version 1.5.6rc3. RMSD values were obtained using Lamarckian Genetic Algorithm and scoring function of AutoDock 4.2 release software.

Results: The activities of the compounds were compared with galantamine as cholinesterase enzyme inhibitor, and some of the compounds showed higher BChE inhibitory activity than galantamine. Compound F111 was shown best BChE inhibitor affect in 50 µM dose, 89.43% inhibition of BChE (IC50=4.27±0.36 µM).

Conclusion: This study supports that novel hydrazone derivates may be used for the development of new BChE inhibitory agents.

Keywords: Alzheimer`s disease, AChE inhibitör, BChE inhibitör, 3(2H)-Pyridazinone, Hydrazone, Molecular docking

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(E-pub Ahead of Print)
DOI: 10.2174/1389557519666191010154444
Price: $95

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