Design, Synthesis, and Evaluation of Novel 2H-Benzo[b][1,4]thiazin-3(4H)-one Derivatives as New Acetylcholinesterase Inhibitors

Creative Commons License

Ali S. H., OSMANİYE D., SAĞLIK B. N., LEVENT S., ÖZKAY Y., KAPLANCIKLI Z. A.

MOLECULES, cilt.27, sa.7, 2022 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 27 Sayı: 7
  • Basım Tarihi: 2022
  • Doi Numarası: 10.3390/molecules27072121
  • Dergi Adı: MOLECULES
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Aerospace Database, Biotechnology Research Abstracts, CAB Abstracts, Chemical Abstracts Core, Communication Abstracts, EMBASE, Food Science & Technology Abstracts, MEDLINE, Metadex, Veterinary Science Database, Directory of Open Access Journals, Civil Engineering Abstracts
  • Anahtar Kelimeler: Alzheimer's disease, thiadiazole, benzothiazine, acetylcholinesterase, molecular docking, antioxidant activity, blood-brain barrier permeability, cytotoxicity, ALZHEIMERS-DISEASE, CHOLINESTERASE-INHIBITORS, DONEPEZIL TREATMENT, STRATEGIES
  • Bilecik Şeyh Edebali Üniversitesi Adresli: Hayır

Özet

Alzheimer's disease (AD) is a slowly progressive neurodegenerative disease that causes dementia in people aged 65 and over. In the present study, a series of thiadiazole hybrid compounds with benzothiazine derivatives as acetylcholinesterase inhibitors were developed and evaluated for their biological activity. The AChE and BChE inhibition potentials of all compounds were evaluated by using the in vitro Ellman method. The biological evaluation showed that compounds 3i and 3j displayed significant inhibitory activity against AChE. Compounds 3i and 3j showed IC50 values of 0.027 mu M and 0.025 mu M against AChE, respectively. The reference drug donepezil (IC50 = 0.021 mu M) also showed significant inhibition against AChE. Further docking simulation also revealed that these compounds (3i and 3j) interacted with the active site of the enzyme similarly to donepezil. The antioxidant study revealed that compounds 3i and 3j exhibited greater antioxidant effects. An in vitro blood-brain barrier permeability study showed that compounds 3i and 3j are promising compounds against AD. The cytotoxicity study of compounds 3i and 3j showed non-cytotoxic with an IC50 value of 98.29 +/- 3.98 mu M and 159.68 +/- 5.53 mu M against NIH/3T3 cells, respectively.