Design, synthesis and biological evaluation of new benzoxazolone/benzothiazolone derivatives as multi-target agents against Alzheimer's disease

Erdogan M., Kılıç B., Sagkan R. I., Aksakal F., Ercetin T., Gulcan H. O., ...More

European Journal of Medicinal Chemistry, vol.212, 2021 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 212
  • Publication Date: 2021
  • Doi Number: 10.1016/j.ejmech.2020.113124
  • Journal Name: European Journal of Medicinal Chemistry
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, BIOSIS, CAB Abstracts, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE, Veterinary Science Database
  • Keywords: Alzheimer's disease, Benzoxazolone, Benzothiazolone, Cholinesterase inhibitory activity, Anti-inflammatory, Molecular docking, TARGET-DIRECTED LIGANDS, ACETYLCHOLINESTERASE INHIBITORS, MONOAMINE-OXIDASE, OXIDATIVE STRESS, NEUROINFLAMMATION, PATHOPHYSIOLOGY, ANTIOXIDANT, APOPTOSIS, DONEPEZIL, ASSAY
  • Gazi University Affiliated: Yes


In this study, four series of compounds with benzoxazolone and benzothiazolone cores were designed, synthesized and evaluated as multifunctional agents against Alzheimer's disease (AD). Additionally, in order to shed light on the effect of the carbonyl groups of benzoxazolone/benzothiazolone, benzoxazole/benzothiazole-containing analogues were also synthesized and evaluated. Inhibition potency of all final compounds towards cholinesterase enzymes and their antioxidant activity were tested. Subsequently, the anti-inflammatory activity, cytotoxicity, apoptosis, and Aβ aggregation inhibition tests were also performed for selected compounds. The results indicated that compounds 11c, a pentanamide derivative with benzothiazolone core, and 14b, a keton derivative with benzothiazolone core, were considered as promising multi-functional agents for further investigation against AD. The reversibility, kinetic and molecular docking studies were also performed for the compounds with the highest AChE 14b (eeAChE IC50 = 0.34 μM, huAChE IC50 = 0.46 μM) and BChE 11c (eqBChE IC50 = 2.98 μM, huBChE IC50 = 2.56 μM) inhibitory activities.