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Aromatase inhibitors and antiepileptic drugs: a computational systems biology analysis

BACKGROUND: The present study compares antiepileptic drugs and aromatase (CYP19) inhibitors for chemical and structural similarity. Human aromatase is well known as an important pharmacological target in anti-breast cancer therapy, but recent research demonstrates its role in epileptic seizures, as...

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Autores principales: Muftuoglu, Yagmur, Mustata, Gabriela
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129585/
https://www.ncbi.nlm.nih.gov/pubmed/21693043
http://dx.doi.org/10.1186/1477-7827-9-92
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author Muftuoglu, Yagmur
Mustata, Gabriela
author_facet Muftuoglu, Yagmur
Mustata, Gabriela
author_sort Muftuoglu, Yagmur
collection PubMed
description BACKGROUND: The present study compares antiepileptic drugs and aromatase (CYP19) inhibitors for chemical and structural similarity. Human aromatase is well known as an important pharmacological target in anti-breast cancer therapy, but recent research demonstrates its role in epileptic seizures, as well. The current antiepileptic treatment methods cause severe side effects that endanger patient health and often preclude continued use. As a result, less toxic and more tolerable antiepileptic drugs (AEDs) are needed, especially since every individual responds differently to given treatment options. METHODS: Through a pharmacophore search, this study shows that a model previously designed to search for new classes of aromatase inhibitors is able to identify antiepileptic drugs from the set of drugs approved by the Food and Drug Administration. Chemical and structural similarity analyses were performed using five potent AIs, and these studies returned a set of AEDs that the model identifies as hits. RESULTS: The pharmacophore model returned 73% (19 out of 26) of the drugs used specifically to treat epilepsy and approximately 82% (51 out of 62) of the compounds with anticonvulsant properties. Therefore, this study supports the possibility of identifying AEDs with a pharmacophore model that had originally been designed to identify new classes of aromatase inhibitors. Potential candidates for anticonvulsant therapy identified in this manner are also reported. Additionally, the chemical and structural similarity between antiepileptic compounds and aromatase inhibitors is proved using similarity analyses. CONCLUSIONS: This study demonstrates that a pharmacophore search using a model based on aromatase inhibition and the enzyme's structural features can be used to screen for new candidates for antiepileptic therapy. In fact, potent aromatase inhibitors and current antiepileptic compounds display significant - over 70% - chemical and structural similarity, and the similarity analyses performed propose a number of antiepileptic compounds with high potential for aromatase inhibition.
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spelling pubmed-31295852011-07-06 Aromatase inhibitors and antiepileptic drugs: a computational systems biology analysis Muftuoglu, Yagmur Mustata, Gabriela Reprod Biol Endocrinol Research BACKGROUND: The present study compares antiepileptic drugs and aromatase (CYP19) inhibitors for chemical and structural similarity. Human aromatase is well known as an important pharmacological target in anti-breast cancer therapy, but recent research demonstrates its role in epileptic seizures, as well. The current antiepileptic treatment methods cause severe side effects that endanger patient health and often preclude continued use. As a result, less toxic and more tolerable antiepileptic drugs (AEDs) are needed, especially since every individual responds differently to given treatment options. METHODS: Through a pharmacophore search, this study shows that a model previously designed to search for new classes of aromatase inhibitors is able to identify antiepileptic drugs from the set of drugs approved by the Food and Drug Administration. Chemical and structural similarity analyses were performed using five potent AIs, and these studies returned a set of AEDs that the model identifies as hits. RESULTS: The pharmacophore model returned 73% (19 out of 26) of the drugs used specifically to treat epilepsy and approximately 82% (51 out of 62) of the compounds with anticonvulsant properties. Therefore, this study supports the possibility of identifying AEDs with a pharmacophore model that had originally been designed to identify new classes of aromatase inhibitors. Potential candidates for anticonvulsant therapy identified in this manner are also reported. Additionally, the chemical and structural similarity between antiepileptic compounds and aromatase inhibitors is proved using similarity analyses. CONCLUSIONS: This study demonstrates that a pharmacophore search using a model based on aromatase inhibition and the enzyme's structural features can be used to screen for new candidates for antiepileptic therapy. In fact, potent aromatase inhibitors and current antiepileptic compounds display significant - over 70% - chemical and structural similarity, and the similarity analyses performed propose a number of antiepileptic compounds with high potential for aromatase inhibition. BioMed Central 2011-06-21 /pmc/articles/PMC3129585/ /pubmed/21693043 http://dx.doi.org/10.1186/1477-7827-9-92 Text en Copyright ©2011 Muftuoglu and Mustata; 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
Muftuoglu, Yagmur
Mustata, Gabriela
Aromatase inhibitors and antiepileptic drugs: a computational systems biology analysis
title Aromatase inhibitors and antiepileptic drugs: a computational systems biology analysis
title_full Aromatase inhibitors and antiepileptic drugs: a computational systems biology analysis
title_fullStr Aromatase inhibitors and antiepileptic drugs: a computational systems biology analysis
title_full_unstemmed Aromatase inhibitors and antiepileptic drugs: a computational systems biology analysis
title_short Aromatase inhibitors and antiepileptic drugs: a computational systems biology analysis
title_sort aromatase inhibitors and antiepileptic drugs: a computational systems biology analysis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3129585/
https://www.ncbi.nlm.nih.gov/pubmed/21693043
http://dx.doi.org/10.1186/1477-7827-9-92
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