Current Computer-Aided Drug Design

Subhash C. Basak
Departments of Chemistry, Biochemistry & Molecular Biology University of Minnesota Duluth
Duluth, MN 55811


Pharmacophore Modeling, Virtual and In Vitro Screening for Acetylcholinesterase Inhibitors and their Effects on Amyloid-β Self- Assembly

Author(s): Seema Bag, Rekha Tulsan, Abha Sood, Silpi Datta, Marianna Torok.


One of the most promising methods of unveiling the pharmacology of marketed drugs is to screen them against new biological targets. In an attempt to find inhibitors for acetylcholinesterase (AChE), the Drug Bank Database and natural alkaloids with other known medicinal values were screened through a four-point pharmacophore built in this study. The development of the pharmacophore was based on a structurally diverse set of reported AChE inhibitors and was validated using a separate set of known inhibitors. The developed pharmacophore indicated that the presence of one H-acceptor motif, one H-donor motif, one positively charged group and one aromatic ring is needed for AChE inhibition. Selected hits were further investigated by molecular docking and in vitro testing. The assays revealed that the majority of these compounds showed reasonable inhibition, indicating that the developed pharmacophore can indeed reliably screen molecules for potential AChE inhibitors. It appears that several commercially available marketed drugs have further potential as AChE inhibitors. To extend our study the same compounds have been tested in the fibrillogenesis inhibition of amyloid β (Aβ) peptide to explore the possibility of their dual-function therapeutic activity in Alzheimer’s disease.

Keywords: Alzheimer’s disease, acetylcholinesterase, AChE inhibitors, pharmacophore, docking, amyloid β self-assembly, drug bank database, alkaloids, Schrödinger

Order Reprints Order Eprints Rights & PermissionsPrintExport

Article Details

Year: 2013
Page: [2 - 14]
Pages: 13
DOI: 10.2174/1573409911309010002