New applications for known drugs: Human glycogen synthase kinase 3 inhibitors as modulators of Aspergillus fumigatus growth

Invasive aspergillosis (IA) is one of the most severe forms of fungi infection. IA disease is mainly due to Aspergillus fumigatus, an air-borne opportunistic pathogen. Mortality rate caused by IA is still very high (50-95%), because of difficulty in early diagnostics and reduced antifungal treatment...

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Authors: Sebastián-Pérez, Víctor, Manoli, Maria-Tsampika, Pérez, Daniel I, Gil, Carmen, Mellado, Emilia, Martínez, Ana, Espeso, Eduardo A, Campillo, Nuria E
Format: article
Publication Date:2016
Country:España
Institution:Instituto de Salud Carlos III (ISCIII)
Repository:Repisalud
Language:English
OAI Identifier:oai:repisalud.isciii.es:20.500.12105/13889
Online Access:http://hdl.handle.net/20.500.12105/13889
Access Level:Open access
Keyword:Drug Repositioning
Amino Acid Sequence
Antifungal Agents
Aspergillus fumigatus
Enzyme Inhibitors
Glycogen Synthase Kinase 3
Humans
Molecular Docking Simulation
Protein Conformation
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spelling New applications for known drugs: Human glycogen synthase kinase 3 inhibitors as modulators of Aspergillus fumigatus growthSebastián-Pérez, VíctorManoli, Maria-TsampikaPérez, Daniel IGil, CarmenMellado, EmiliaMartínez, AnaEspeso, Eduardo ACampillo, Nuria EDrug RepositioningAmino Acid SequenceAntifungal AgentsAspergillus fumigatusEnzyme InhibitorsGlycogen Synthase Kinase 3HumansMolecular Docking SimulationProtein ConformationInvasive aspergillosis (IA) is one of the most severe forms of fungi infection. IA disease is mainly due to Aspergillus fumigatus, an air-borne opportunistic pathogen. Mortality rate caused by IA is still very high (50-95%), because of difficulty in early diagnostics and reduced antifungal treatment options, thus new and efficient drugs are necessary. The aim of this work is, using Aspergillus nidulans as non-pathogen model, to develop efficient drugs to treat IA. The recent discovered role of glycogen synthase kinase-3 homologue, GskA, in A. fumigatus human infection and our previous experience on human GSK-3 inhibitors focus our attention on this kinase as a target for the development of antifungal drugs. With the aim to identify effective inhibitors of colonial growth of A. fumigatus we use A. nidulans as an accurate model for in vivo and in silico studies. Several well-known human GSK-3β inhibitors were tested for inhibition of A. nidulans colony growth. Computational tools as docking studies and binding site prediction was used to explain the different biological profile of the tested inhibitors. Three of the five tested hGSK3β inhibitors are able to reduce completely the colonial growth by covalent bind to the enzyme. Therefore these compounds may be useful in different applications to eradicate IA.Elsevier20222022-03-2920162016-06-0120162016-06-01journal articlehttp://purl.org/coar/resource_type/c_6501AMhttp://purl.org/coar/version/c_ab4af688f83e57aainfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/20.500.12105/13889reponame:Repisaludinstname:Instituto de Salud Carlos III (ISCIII)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2Attribution-NonCommercial-NoDerivatives 4.0 Internacionalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:repisalud.isciii.es:20.500.12105/138892026-06-12T12:43:37Z
dc.title.none.fl_str_mv New applications for known drugs: Human glycogen synthase kinase 3 inhibitors as modulators of Aspergillus fumigatus growth
title New applications for known drugs: Human glycogen synthase kinase 3 inhibitors as modulators of Aspergillus fumigatus growth
spellingShingle New applications for known drugs: Human glycogen synthase kinase 3 inhibitors as modulators of Aspergillus fumigatus growth
Sebastián-Pérez, Víctor
Drug Repositioning
Amino Acid Sequence
Antifungal Agents
Aspergillus fumigatus
Enzyme Inhibitors
Glycogen Synthase Kinase 3
Humans
Molecular Docking Simulation
Protein Conformation
title_short New applications for known drugs: Human glycogen synthase kinase 3 inhibitors as modulators of Aspergillus fumigatus growth
title_full New applications for known drugs: Human glycogen synthase kinase 3 inhibitors as modulators of Aspergillus fumigatus growth
title_fullStr New applications for known drugs: Human glycogen synthase kinase 3 inhibitors as modulators of Aspergillus fumigatus growth
title_full_unstemmed New applications for known drugs: Human glycogen synthase kinase 3 inhibitors as modulators of Aspergillus fumigatus growth
title_sort New applications for known drugs: Human glycogen synthase kinase 3 inhibitors as modulators of Aspergillus fumigatus growth
dc.creator.none.fl_str_mv Sebastián-Pérez, Víctor
Manoli, Maria-Tsampika
Pérez, Daniel I
Gil, Carmen
Mellado, Emilia
Martínez, Ana
Espeso, Eduardo A
Campillo, Nuria E
author Sebastián-Pérez, Víctor
author_facet Sebastián-Pérez, Víctor
Manoli, Maria-Tsampika
Pérez, Daniel I
Gil, Carmen
Mellado, Emilia
Martínez, Ana
Espeso, Eduardo A
Campillo, Nuria E
author_role author
author2 Manoli, Maria-Tsampika
Pérez, Daniel I
Gil, Carmen
Mellado, Emilia
Martínez, Ana
Espeso, Eduardo A
Campillo, Nuria E
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv
dc.subject.none.fl_str_mv Drug Repositioning
Amino Acid Sequence
Antifungal Agents
Aspergillus fumigatus
Enzyme Inhibitors
Glycogen Synthase Kinase 3
Humans
Molecular Docking Simulation
Protein Conformation
topic Drug Repositioning
Amino Acid Sequence
Antifungal Agents
Aspergillus fumigatus
Enzyme Inhibitors
Glycogen Synthase Kinase 3
Humans
Molecular Docking Simulation
Protein Conformation
description Invasive aspergillosis (IA) is one of the most severe forms of fungi infection. IA disease is mainly due to Aspergillus fumigatus, an air-borne opportunistic pathogen. Mortality rate caused by IA is still very high (50-95%), because of difficulty in early diagnostics and reduced antifungal treatment options, thus new and efficient drugs are necessary. The aim of this work is, using Aspergillus nidulans as non-pathogen model, to develop efficient drugs to treat IA. The recent discovered role of glycogen synthase kinase-3 homologue, GskA, in A. fumigatus human infection and our previous experience on human GSK-3 inhibitors focus our attention on this kinase as a target for the development of antifungal drugs. With the aim to identify effective inhibitors of colonial growth of A. fumigatus we use A. nidulans as an accurate model for in vivo and in silico studies. Several well-known human GSK-3β inhibitors were tested for inhibition of A. nidulans colony growth. Computational tools as docking studies and binding site prediction was used to explain the different biological profile of the tested inhibitors. Three of the five tested hGSK3β inhibitors are able to reduce completely the colonial growth by covalent bind to the enzyme. Therefore these compounds may be useful in different applications to eradicate IA.
publishDate 2016
dc.date.none.fl_str_mv 2016
2016-06-01
2016
2016-06-01
2022
2022-03-29
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
AM
http://purl.org/coar/version/c_ab4af688f83e57aa
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv http://hdl.handle.net/20.500.12105/13889
url http://hdl.handle.net/20.500.12105/13889
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
http://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier
publisher.none.fl_str_mv Elsevier
dc.source.none.fl_str_mv reponame:Repisalud
instname:Instituto de Salud Carlos III (ISCIII)
instname_str Instituto de Salud Carlos III (ISCIII)
reponame_str Repisalud
collection Repisalud
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869410114315747328
score 15,228081

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