Design and synthesis of ranitidine analogs as multi-target directed ligands for the treatment of alzheimer’s disease

Jie Gao, Chen Suo, Jui Heng Tseng, Melissa A. Moss, Alvin V. Terry, James Chapman

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

The aggregation of amyloid β (Aβ) peptides and deposition of amyloid plaques are implicated in the pathogenesis of Alzheimer’s disease (AD). Therefore, blocking Aβ aggregation with small molecules has been proposed as one therapeutic approach for AD. In the present study, a series of ranitidine analogs containing cyclic imide isosteres were synthesized and their inhibitory activities toward Aβ aggregation were evaluated using in vitro thioflavin T assays. The structure– activity relationship revealed that the 1,8-naphthalimide moiety provided profound inhibition of Aβ aggregation and structural modifications on the other parts of the parent molecule (compound 6) maintained similar efficacy. Some of these ranitidine analogs also possessed potent inhibitory activities of acetylcholinesterase (AChE), which is another therapeutic target in AD. These ranitidine analogs, by addressing both Aβ aggregation and AChE, offer insight into the key chemical features of a new type of multi-target directed ligands for the pharmaceutical treatment of AD.

Original languageEnglish (US)
Article number3120
Pages (from-to)1-9
Number of pages9
JournalInternational journal of molecular sciences
Volume22
Issue number6
DOIs
StatePublished - Mar 2 2021

Keywords

  • Acetylcholinesterase
  • Alzheimer’s disease
  • Amyloid β (Aβ) aggregation
  • Multi-target directed ligands
  • Naphthalimide
  • Thioflavin T

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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