Journal of Molecular Modeling

, Volume 19, Issue 3, pp 1179–1194

In vitro inhibitory profile of NDGA against AChE and its in silico structural modifications based on ADME profile

Authors

  • Chandran Remya
    • Department of Biotechnology and Microbiology and Inter University Centre for BiosciencesKannur University
  • Kalarickal Vijayan Dileep
    • Department of Biotechnology and Microbiology and Inter University Centre for BiosciencesKannur University
  • Ignatius Tintu
    • Department of Biotechnology and Microbiology and Inter University Centre for BiosciencesKannur University
  • Elessery Jayadevi Variyar
    • Department of Biotechnology and Microbiology and Inter University Centre for BiosciencesKannur University
    • Department of Biotechnology and Microbiology and Inter University Centre for BiosciencesKannur University
Original Paper

DOI: 10.1007/s00894-012-1656-0

Cite this article as:
Remya, C., Dileep, K.V., Tintu, I. et al. J Mol Model (2013) 19: 1179. doi:10.1007/s00894-012-1656-0

Abstract

Acetylcholinesterase (AChE) inhibitors are currently in focus for the pharmacotherapy of Alzheimer’s disease (AD). These inhibitors increase the level of acetylcholine in the brain and facilitate cholinergic neurotransmission. AChE inhibitors such as rivastigmine, galantamine, physostigmine and huperzine are obtained from plants, indicating that plants can serve as a potential source for novel AChE inhibitors. We have performed a virtual screening of diverse natural products with distinct chemical structure against AChE. NDGA was one among the top scored compounds and was selected for enzyme kinetic studies. The IC50 of NDGA on AChE was 46.2 μM. However, NDGA showed very poor central nervous system (CNS) activity and blood–brain barrier (BBB) penetration. In silico structural modification on NDGA was carried out in order to obtain derivatives with better CNS activity as well as BBB penetration. The studies revealed that some of the designed compounds can be used as lead molecules for the development of drugs against AD

https://static-content.springer.com/image/art%3A10.1007%2Fs00894-012-1656-0/MediaObjects/894_2012_1656_Figa_HTML.gif
Figure

Inhibitory activity of NDGA against AChE

Keywords

AcetylcholinesteraseNDGAADMECNS activityInduced fit docking

Copyright information

© Springer-Verlag Berlin Heidelberg 2012