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A new strategy based on pharmacophore-based virtual screening in adenosine deaminase inhibitors detection and in-vitro study
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 inhibitor...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2012
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556010/ https://www.ncbi.nlm.nih.gov/pubmed/23351306 http://dx.doi.org/10.1186/2008-2231-20-64 |
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author | Bazl, Roya Ganjali, Mohammad Reza Saboury, Ali-akbar Foroumadi, Alireza Nourozi, Parviz Amanlou, Massoud |
author_facet | Bazl, Roya Ganjali, Mohammad Reza Saboury, Ali-akbar Foroumadi, Alireza Nourozi, Parviz Amanlou, Massoud |
author_sort | Bazl, Roya |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-3556010 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2012 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-35560102013-01-31 A new strategy based on pharmacophore-based virtual screening in adenosine deaminase inhibitors detection and in-vitro study Bazl, Roya Ganjali, Mohammad Reza Saboury, Ali-akbar Foroumadi, Alireza Nourozi, Parviz Amanlou, Massoud Daru Research Article 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. BioMed Central 2012-10-22 /pmc/articles/PMC3556010/ /pubmed/23351306 http://dx.doi.org/10.1186/2008-2231-20-64 Text en Copyright ©2012 Bazl et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Bazl, Roya Ganjali, Mohammad Reza Saboury, Ali-akbar Foroumadi, Alireza Nourozi, Parviz Amanlou, Massoud A new strategy based on pharmacophore-based virtual screening in adenosine deaminase inhibitors detection and in-vitro study |
title | A new strategy based on pharmacophore-based virtual screening in adenosine deaminase inhibitors detection and in-vitro study |
title_full | A new strategy based on pharmacophore-based virtual screening in adenosine deaminase inhibitors detection and in-vitro study |
title_fullStr | A new strategy based on pharmacophore-based virtual screening in adenosine deaminase inhibitors detection and in-vitro study |
title_full_unstemmed | A new strategy based on pharmacophore-based virtual screening in adenosine deaminase inhibitors detection and in-vitro study |
title_short | A new strategy based on pharmacophore-based virtual screening in adenosine deaminase inhibitors detection and in-vitro study |
title_sort | new strategy based on pharmacophore-based virtual screening in adenosine deaminase inhibitors detection and in-vitro study |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3556010/ https://www.ncbi.nlm.nih.gov/pubmed/23351306 http://dx.doi.org/10.1186/2008-2231-20-64 |
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