Neurotoxicity Research

, Volume 27, Issue 3, pp 314–327 | Cite as

Protective Effects of a Piperazine Derivative [N-{4-[4-(2-methoxy-phenyl)-piperazin-1-yl]-phenyl} Carbamic Acid Ethyl Ester] Against Aluminium-Induced Neurotoxicity: Insights From In Silico and In Vivo Studies

  • Poonam Meena
  • Apra Manral
  • Vikas Saini
  • Manisha TiwariEmail author
Original Article


The cholinergic hypothesis associated with Alzheimer’s disease has spurred the development of numerous structural classes of compounds with different pharmacological profiles aimed at increasing central cholinergic neurotransmission. In the present study, six synthetic piperazine derivatives D1–D6 were screened for their efficacy as acetylcholinesterase inhibitors (AChEIs) through in silico and in vitro studies. Compound D2 was found to be a potential AChEI with adequate pharmacokinetic properties, as supported by in silico study. Further, in vivo studies were designed to examine the protective effect of piperazine derivative D2 (3 and 5 mg/kg for 6 weeks) in ameliorating the alterations induced by aluminium chloride (AlCl3) on behavioural and neurochemical indices. Behavioural tests (Morris water maze and elevated plus maze) revealed significant alterations in the short-term memory and anxiety levels in rats treated with AlCl3, which was further improved after D2 treatment. Further, D2 treatment attenuated the neurotoxic effects of AlCl3 as shown by the improvement in rats performance in Water maze test and in lowering AChE activity. Besides preventing lipid peroxidation and protein damage, changes in the levels of endogenous antioxidant enzymes (GST, GPx, GR and GSH) associated with AlCl3 administration were also restored upon treatment with D2. Thus, our results support the neuroprotective potential of compound D2, thus validating its use in alleviating toxic effects of aluminium.


Acetylcholinesterase Molecular docking Aluminium Neurotoxicity Oxidative stress Neuroprotective 



The authors wish to acknowledge the financial assistance provided by the Department of Science & Technology, Government of India and the facilities provided by University of Delhi. The author Ms. Poonam Meena wishes to acknowledge the award of the Rajiv Gandhi National Fellowship from the University Grants Commission. Scientific contributions from Prof. Vani Brahmachari are gratefully acknowledged. The authors wish to acknowledge the Bioinformatics facility of ACBR.

Conflict of interest

The authors declare that there is no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Poonam Meena
    • 1
  • Apra Manral
    • 1
  • Vikas Saini
    • 1
  • Manisha Tiwari
    • 1
    Email author
  1. 1.Bio-Organic Chemistry Laboratory, Dr. B. R. Ambedkar Centre for Biomedical ResearchUniversity of DelhiDelhiIndia

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