A new series of pyridazinone derivatives as cholinesterases inhibitors: Synthesis, in vitro activity and molecular modeling studies


Özçelik A. B. , Özdemir Z., Sarı S., Utku S., Uysal M.

PHARMACOLOGICAL REPORTS, vol.71, no.6, pp.1253-1263, 2019 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 71 Issue: 6
  • Publication Date: 2019
  • Doi Number: 10.1016/j.pharep.2019.07.006
  • Journal Name: PHARMACOLOGICAL REPORTS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.1253-1263
  • Keywords: AChE inhibitor, BChE inhibitor, 3(2H)-Pyridazinone, Hydrazone, Molecular modelling, ALZHEIMERS-DISEASE, HUMAN ACETYLCHOLINESTERASE, ANTIINFLAMMATORY ACTIVITY, ACCURATE DOCKING, PERIPHERAL SITE, BUTYRYLCHOLINESTERASE, PROTEIN, DESIGN, GLIDE, TAUTOMERISM
  • Gazi University Affiliated: Yes

Abstract

Background: The pyridazinone nucleus has been incorporated into a wide variety of therapeutically interesting molecules to transform them into better drugs. Acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) are known to be serine hydrolase enzymes responsible for the hydrolysis of acetylcholine (ACh). Inhibition of cholinesterases is an effective method to curb Alzheimer's disease. Here, we prepared 12 new 6-substituted-3(2H)-pyridazinone-2-acetyl-2-(nonsubstituted/4-substituted benzenesulfonohydrazide) derivatives and evaluated their inhibitory effects on AChE/BChE in pursuit of potent dual inhibitors for Alzheirmer's Disease. 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.