Design, Synthesis, and Biological Activity Evaluation of New Donepezil-Like Compounds Bearing Thiazole Ring for the Treatment of Alzheimer's Disease

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CRYSTALS, vol.10, no.8, 2020 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 10 Issue: 8
  • Publication Date: 2020
  • Doi Number: 10.3390/cryst10080637
  • Journal Name: CRYSTALS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Aerospace Database, Applied Science & Technology Source, Communication Abstracts, Computer & Applied Sciences, INSPEC, Metadex, Directory of Open Access Journals, Civil Engineering Abstracts
  • Keywords: Alzheimer's disease, anticholinesterase enzyme activity, beta amyloid plaque inhibition, donepezil, molecular docking, thiazolylhydrazone, BENZYL PYRIDINIUM MOIETY, ACETYLCHOLINESTERASE INHIBITORS, DERIVATIVES, BINDING, SOLUBILITY, DOCKING, POTENT
  • Anadolu University Affiliated: Yes


Alzheimer's disease (AD) is a progressive and neurodegenerative disease that is primarily seen in the elderly population and is clinically characterized by memory and cognitive impairment. The importance of the disease has increased as a result of etiology of the disease having not yet been determined, an increase in patient population over the years, absence of radical treatment, high cost of treatment and care, and significant reduction in the quality of life of the patients, which have led researchers to direct more attention to this field. In a recent study, new indan-thiazolylhydrazone derivatives were designed and synthesized based on the chemical structure of the donepezil molecule, which is the most preferred and has the most appropriate response in the treatment of AD. The structures of the compounds were determined by(1)H-NMR and(13)C-NMR, and mass spectroscopic methods. Inhibition studies on the cholinesterase (ChE) enzymes and beta amyloid plaque inhibition test of the compounds were performed. Among the synthesized derivatives, compounds2a,2e,2i, and2lshowed potent inhibitory activity on the AChE enzyme. Compound2ewas found to be the most active agent, with an IC(50)value of 0.026 mu M. The mechanism of AChE inhibition by compound2ewas studied using the Lineweaver-Burk plot, and the nature of inhibition was also determined to be mix-typed. Molecular docking studies were also carried out for compound2e, which was found as the most potent agent within the AChE enzyme active site. Moreover, compounds2a,2e,2i, and2ldisplayed the ability to prevent beta amyloid plaque aggregation at varying rates. In addition, ADME (Absorption, Distribution, Metabolism, Elimination) parameters were evaluated for all synthesized compounds using theQikProp 4.8software (Schrodinger Inc., NY, USA).