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Open Access Research article

A new strategy based on pharmacophore-based virtual screening in adenosine deaminase inhibitors detection and in-vitro study

Roya Bazl13, Mohammad Reza Ganjali1, Ali-akbar Saboury2, Alireza Foroumadi3, Parviz Nourozi1 and Massoud Amanlou3*

Author Affiliations

1 Center of Excellence in Electrochemistry, Faculty of Chemistry, University of Tehran, Tehran, Iran

2 Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran

3 Department of Medicinal Chemistry, Faculty of Pharmacy, Drug Design & Development Research Center, Tehran University of Medical Sciences, Tehran, Iran

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DARU Journal of Pharmaceutical Sciences 2012, 20:64  doi:10.1186/2008-2231-20-64

Published: 22 October 2012

Abstract

Background and the purpose of the study

Adenosine deaminase (ADA) inhibition not only may be applied for the treatment of ischemic injury, hypertension, lymphomas and leukaemia, but also they have been considered as anti- inflammatory drugs. On the other hand according to literatures, ADA inhibitors without a nucleoside framework would improve pharmacokinetics and decrease toxicity. Hence we have carried out a rational pharmacophore design for non-nucleoside inhibitors filtration.

Methods

A merged pharmacophore model based on the most potent non-nucleoside inhibitor erythro-9-(2-hydroxy-3-nonyl) adenine (EHNA) and natural products were generated and applied for compounds filtration. The effects of filtrated compounds based on pharmacophore and docking studies investigated on ADA by UV and Fluorescence spectroscopy techniques.

Results

Extracted compounds were find efficiently inhibit ADA, and the most potent (2) shows an inhibition constant equal to 20 μM. Besides, Fluorescence spectroscopy studies revealed that enzyme 3D structure bear further change in lower concentrations of compound 2.

Conclusion

3 non-nucleoside inhibitors for ADA are presented. According to obtained results from UV and fluorescence spectroscopy, such interesting pharmacophore template with multiple approaches will help us to extract or design compound with desired properties.

Keywords:
Adenosine deaminase; Pharmachophore; Docking; Lead discovery, Inhibitor