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, cilt.71, sa.6, ss.1253-1263, 2019 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 71 Sayı: 6
  • Basım Tarihi: 2019
  • Doi Numarası: 10.1016/j.pharep.2019.07.006
  • Dergi Adı: PHARMACOLOGICAL REPORTS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.1253-1263
  • Anahtar Kelimeler: 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 Üniversitesi Adresli: Evet

Özet

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.