Multifunctional quinoxaline-hydrazone derivatives with acetylcholinesterase and monoamine oxidases inhibitory activities as potential agents against Alzheimer's disease

Cevik U., OSMANİYE D., SAĞLIK B. N., KAYA ÇAVUŞOĞLU B., LEVENT S., KARADUMAN A. B., ...Daha Fazla

MEDICINAL CHEMISTRY RESEARCH, cilt.29, sa.6, ss.1000-1011, 2020 (SCI-Expanded) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 29 Sayı: 6
  • Basım Tarihi: 2020
  • Doi Numarası: 10.1007/s00044-020-02541-4
  • Dergi Adı: MEDICINAL CHEMISTRY RESEARCH
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chimica, EMBASE, Veterinary Science Database
  • Sayfa Sayıları: ss.1000-1011
  • Anahtar Kelimeler: Quinoxaline-hydrazone, Acetylcholinesterase, Butyrylcholinesterase, Monoamine oxidases, Enzyme inhibition, BIOLOGICAL EVALUATION, DUAL INHIBITORS, DESIGN, ACHE, MAO, PROPARGYLAMINE, DISCOVERY, COMPLEX
  • Anadolu Üniversitesi Adresli: Evet

Özet

Multitarget molecules are considered as an effective way for the treatment of AD, instead of the classic one-drug-one-target strategy because of the multifactorial nature of AD. A variety of studies indicate that several enzymes inhibitors can be useful in the treatment of AD, including acetylcholinesterase (AchE), butyrylcholinesterase (BuChE) and monoamine oxidase (MAO). Various substituted quinoxaline-hydrazone derivatives were synthesized, and their activity in vitro were investigated, including AChE/BuChE inhibitory activity and MAOA/B inhibitory activity. Based on the experimental results, compound 5l exhibited good inhibitory potency on both AchE (IC50 = 0.028 +/- 0.001 mu M) and monoamine oxidase B (IC50 = 0.046 +/- 0.002 mu M). Molecular modeling studies showed that 5l could bind to the active site of AChE and MAO-B. Taken together, these results suggested that compound 5l might be a potential multifunctional agent for the treatment of AD.