Synthesis and anticholinesterase activity of huperzine a analogues containing phenol and catechol replacements for the pyridone ring

Giuseppe Campiani, Alan P. Kozikowski, Shaomeng Wang, Liu Ming, Vito Nacci, Ashima Saxena, Bhupendra P. Doctor

Research output: Contribution to journalArticlepeer-review

Abstract

Based upon modeling results obtained using the crystal structure of huperzine A in complex with acetylcholinesterase (AChE), two novel analogues of this potent AChE inhibitor were designed with phenol or catechol rings replacing the pyridone ring. From the modeling studies, the catechol analogue appeared capable of replacing one of the crystallographic waters bridging huperzine with Tyr 130 and Glu 199 of AChE. The synthesis of these materials by use of a palladium catalyzed bicycloannulation strategy is detailed together with the results of AChE inhibition assays.

Original languageEnglish (US)
Pages (from-to)1413-1418
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume8
Issue number11
DOIs
StatePublished - Jun 2 1998

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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