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


ÇEVİK U. A. , OSMANİYE D., SAĞLIK B. N. , Cavusoglu B. K. , LEVENT S., KARADUMAN A. B. , ...More

MEDICINAL CHEMISTRY RESEARCH, vol.29, no.6, pp.1000-1011, 2020 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 29 Issue: 6
  • Publication Date: 2020
  • Doi Number: 10.1007/s00044-020-02541-4
  • Journal Name: MEDICINAL CHEMISTRY RESEARCH
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CAB Abstracts, Chimica, EMBASE, Veterinary Science Database
  • Page Numbers: pp.1000-1011
  • Eskisehir Osmangazi University Affiliated: No

Abstract

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.