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Ginger components as new leads for the design and development of novel multi-targeted anti-Alzheimer’s drugs: a computational investigation

Authors Azam F, Amer AM, Abulifa AR, Elzwawi MM

Received 15 May 2014

Accepted for publication 20 June 2014

Published 23 October 2014 Volume 2014:8 Pages 2045—2059

DOI https://doi.org/10.2147/DDDT.S67778

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Faizul Azam,1,2 Abdualrahman M Amer,1 Abdullah R Abulifa,1 Mustafa M Elzwawi1

1Faculty of Pharmacy, Misurata University, Misurata, Libya; 2Department of Pharmaceutical Chemistry, Nims Institute of Pharmacy, Nims University, Jaipur, Rajasthan, India

Abstract: Ginger (Zingiber officinale), despite being a common dietary adjunct that contributes to the taste and flavor of foods, is well known to contain a number of potentially bioactive phytochemicals having valuable medicinal properties. Although recent studies have emphasized their benefits in Alzheimer’s disease, limited information is available on the possible mechanism by which it renders anti-Alzheimer activity. Therefore, the present study seeks to employ molecular docking studies to investigate the binding interactions between active ginger components and various anti-Alzheimer drug targets. Lamarckian genetic algorithm methodology was employed for docking of 12 ligands with 13 different target proteins using AutoDock 4.2 program. Docking protocol was validated by re-docking of all native co-crystallized ligands into their original binding cavities exhibiting a strong correlation coefficient value (r2=0.931) between experimentally reported and docking predicted activities. This value suggests that the approach could be a promising computational tool to aid optimization of lead compounds obtained from ginger. Analysis of binding energy, predicted inhibition constant, and hydrophobic/hydrophilic interactions of ligands with target receptors revealed acetylcholinesterase as most promising, while c-Jun N-terminal kinase was recognized as the least favorable anti-Alzheimer’s drug target. Common structural requirements include hydrogen bond donor/acceptor area, hydrophobic domain, carbon spacer, and distal hydrophobic domain flanked by hydrogen bond donor/acceptor moieties. In addition, drug-likeness score and molecular properties responsible for a good pharmacokinetic profile were calculated by Osiris property explorer and Molinspiration online toolkit, respectively. None of the compounds violated Lipinski’s rule of five, making them potentially promising drug candidates for the treatment of Alzheimer’s disease.

Keywords: Alzheimer’s disease, ginger, molecular docking, structure–activity relationship, toxicity prediction

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