Multifunctional quinoxaline-hydrazone derivatives with acetylcholinesterase and monoamine oxidases inhibitory activities as potential agents against Alzheimer's disease
MEDICINAL CHEMISTRY RESEARCH, cilt.29, sa.6, ss.1000-1011, 2020 (SCI-Expanded, Scopus)
- 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
- Bilecik Şeyh Edebali Üniversitesi Adresli: Hayır
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.