Discovery of potent and selective butyrylcholinesterase inhibitors through the use of pharmacophore-based screening

Alexander Williams, Shuo Zhou, Chang Guo Zhan

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Cholinesterase inhibitors have long been used in the treatment of Alzheimer's Disease (AD) via the protection of acetylcholine levels. However, recent research has shown that the specific inhibition of butyrylcholinesterase (BChE) could better ameliorate symptoms within patients. In addition, it has recently been shown that selective inhibition of BChE can also significantly attenuate the toxicity and physiological effects of heroin. Currently, there are no specific and potent inhibitors of BChE approved for use in AD or heroin abuse. Through a combined use of in silico and in vitro screening, we have found three compounds with sub-50 nM IC50 values that specifically target BChE. These newly discovered BChE inhibitors can act as the lead scaffolds for future development of the desirably potent and selective BChE inhibitors.

Original languageEnglish
Article number126754
JournalBioorganic and Medicinal Chemistry Letters
Volume29
Issue number24
DOIs
StatePublished - Dec 15 2019

Bibliographical note

Publisher Copyright:
© 2019 Elsevier Ltd

Keywords

  • Acetylcholinesterase
  • Butyrylcholinesterase
  • Docking
  • Inhibitor
  • Pharmacophore

ASJC Scopus subject areas

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

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