Synthesis of highly functionalised dispiropyrrolidine derivatives as novel acetylcholinesterase inhibitors

Ang Chee We, Mohamed Ashraf Ali, Yeong Keng Yoon, Rusli Ismail, Tan Soo Choon, Kooi Yeong Khaw, Vikneswaran Murugaiyah, Venu Sanjeevi Lakshmipathi

Research output: Contribution to journalArticleResearchpeer-review

4 Citations (Scopus)

Abstract

In the effort of finding novel acetyl cholinesterase (AChE) inhibitors to improve the efficacy of Alzheimer's disease (AD) treatment, series of substituted aryl-1′-methyldispiro[indan-2,2′ pyrrolidine-3′, 2"-indan]-1,3,1′-trione and substituted 7′-aryl-5′, 6′,7′,7a′-tetrahydrodispiro-[indane-2,5′-pyrrolo[1,2-c] [1,3]thiazole-6′,2"-indan]-1,3,1"-trione analogues were synthesized using [3+2]-cycloaddition reactions. These newly synthesized pyrrolidine compounds were assayed for their biological activity using Ellman's method. The structural elucidation of the compounds was performed by using 1H-NMR, 13C-NMR, ESI-MS spectra and elemental analyses. Eight out of twenty synthesized compounds showed more than 50% inhibition at concentration of 10 μM. Compound 2e, 2i and 3e were among the most active one, giving IC50 value as 3.3 μM for 2e, 3.7 μM for 2i and 5.5 μM for 3e, respectively. Lineweaver-Burk plot indicated that 2i inhibits AChE in a competitive manner. Molecular modelling study was performed to disclose the binding interaction of these compounds with the active site of AChE.

Original languageEnglish
Pages (from-to)156-161
Number of pages6
JournalLetters in Drug Design and Discovery
Volume11
Issue number2
DOIs
Publication statusPublished - Feb 2014
Externally publishedYes

Keywords

  • Acetyl cholinesterase inhibitors
  • Alzheimer's disease
  • Cycloaddition
  • Ellman's method
  • Lineweaver-Burk plot
  • Molecular modeling
  • Pyrrolidine

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