Affiliations 

  • 1 Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, 11800 Penang, Malaysia; School of Science, Monash University Malaysia Campus, Jalan Lagoon Selatan, Bandar Sunway, 47500 Selangor, Malaysia. Electronic address: Yeong.KengYoon@monash.edu
  • 2 Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden, 11800 Penang, Malaysia
  • 3 Institute for Research in Molecular Medicine, Universiti Sains Malaysia, Minden, 11800 Penang, Malaysia
  • 4 Department of Organic Chemistry, School of Chemical Sciences, Universiti Sains Malaysia, Minden, 11800 Penang, Malaysia
Bioorg Chem, 2017 02;70:27-33.
PMID: 27863748 DOI: 10.1016/j.bioorg.2016.11.005

Abstract

A series of novel cholinesterase inhibitors containing nitrobenzoate core structure were synthesized by a facile and efficient method. The structure of the novel compounds were fully characterized and confirmed by analytical as well as spectroscopic methods. Compound indicated as 2f was found to possess the best cholinesterase inhibitory activities of all the evaluated compounds. Results suggest that 2f is a selective acetylcholinesterase inhibitor, although it also inhibits butyrylcholinesterase at higher concentration. Kinetics inhibition result suggest that 2f is a mixed-mode inhibitor of acetylcholinesterase. In addition, it was found to have low cytotoxicity. Molecular docking on compound 2f was carried out to rationalize the observed in vitro enzymatic assay results. Most importantly, the potential of nitrobenzoate derivatives as cholinesterase inhibitor was shown through this study. In summary, we discovered nitrobenzoates as a new scaffold that may eventually yield useful compounds in treatment of Alzheimer's disease.

* Title and MeSH Headings from MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.