Design of Novel N-Myristoyltransferase Inhibitors of Leishmania donovani Using Four-Dimensional Quantitative Structure-Activity Relationship Analysis

Detalhes bibliográficos
Autor(a) principal: Santos-Garcia,Letícia
Data de Publicação: 2018
Outros Autores: Silva,Daniela R., Assis,Letícia C., Assis,Tamiris M. de, Gajo,Giovanna C., Fernandes,Ítalo Antônio, Ramalho,Teodorico C., Cunha,Elaine F. F. da
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Journal of the Brazilian Chemical Society (Online)
Texto Completo: http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532018000701440
Resumo: N-Myristoylation protein is catalyzed by N-myristoyltransferase (NMT), an essential target in Leishmania donovani, the causative agent of kala-azar. Four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis was applied to a series of 77 Leishmania donovani NMT inhibitors. Then, three new compounds were proposed using QSAR models. In addition, molecular docking was performed to predict the binding affinities and interaction modes among the proposed compounds and the NMT active site. In silico absorption, distribution, metabolism and excretion (ADME) evaluation was performed and potential inhibitors demonstrated satisfactory pharmacokinetic properties.
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spelling Design of Novel N-Myristoyltransferase Inhibitors of Leishmania donovani Using Four-Dimensional Quantitative Structure-Activity Relationship Analysisleishmaniasisinhibitors4D-QSARdockingADMEN-Myristoylation protein is catalyzed by N-myristoyltransferase (NMT), an essential target in Leishmania donovani, the causative agent of kala-azar. Four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis was applied to a series of 77 Leishmania donovani NMT inhibitors. Then, three new compounds were proposed using QSAR models. In addition, molecular docking was performed to predict the binding affinities and interaction modes among the proposed compounds and the NMT active site. In silico absorption, distribution, metabolism and excretion (ADME) evaluation was performed and potential inhibitors demonstrated satisfactory pharmacokinetic properties.Sociedade Brasileira de Química2018-07-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532018000701440Journal of the Brazilian Chemical Society v.29 n.7 2018reponame:Journal of the Brazilian Chemical Society (Online)instname:Sociedade Brasileira de Química (SBQ)instacron:SBQ10.21577/0103-5053.20180007info:eu-repo/semantics/openAccessSantos-Garcia,LetíciaSilva,Daniela R.Assis,Letícia C.Assis,Tamiris M. deGajo,Giovanna C.Fernandes,Ítalo AntônioRamalho,Teodorico C.Cunha,Elaine F. F. daeng2018-06-20T00:00:00Zoai:scielo:S0103-50532018000701440Revistahttp://jbcs.sbq.org.brONGhttps://old.scielo.br/oai/scielo-oai.php||office@jbcs.sbq.org.br1678-47900103-5053opendoar:2018-06-20T00:00Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)false
dc.title.none.fl_str_mv Design of Novel N-Myristoyltransferase Inhibitors of Leishmania donovani Using Four-Dimensional Quantitative Structure-Activity Relationship Analysis
title Design of Novel N-Myristoyltransferase Inhibitors of Leishmania donovani Using Four-Dimensional Quantitative Structure-Activity Relationship Analysis
spellingShingle Design of Novel N-Myristoyltransferase Inhibitors of Leishmania donovani Using Four-Dimensional Quantitative Structure-Activity Relationship Analysis
Santos-Garcia,Letícia
leishmaniasis
inhibitors
4D-QSAR
docking
ADME
title_short Design of Novel N-Myristoyltransferase Inhibitors of Leishmania donovani Using Four-Dimensional Quantitative Structure-Activity Relationship Analysis
title_full Design of Novel N-Myristoyltransferase Inhibitors of Leishmania donovani Using Four-Dimensional Quantitative Structure-Activity Relationship Analysis
title_fullStr Design of Novel N-Myristoyltransferase Inhibitors of Leishmania donovani Using Four-Dimensional Quantitative Structure-Activity Relationship Analysis
title_full_unstemmed Design of Novel N-Myristoyltransferase Inhibitors of Leishmania donovani Using Four-Dimensional Quantitative Structure-Activity Relationship Analysis
title_sort Design of Novel N-Myristoyltransferase Inhibitors of Leishmania donovani Using Four-Dimensional Quantitative Structure-Activity Relationship Analysis
author Santos-Garcia,Letícia
author_facet Santos-Garcia,Letícia
Silva,Daniela R.
Assis,Letícia C.
Assis,Tamiris M. de
Gajo,Giovanna C.
Fernandes,Ítalo Antônio
Ramalho,Teodorico C.
Cunha,Elaine F. F. da
author_role author
author2 Silva,Daniela R.
Assis,Letícia C.
Assis,Tamiris M. de
Gajo,Giovanna C.
Fernandes,Ítalo Antônio
Ramalho,Teodorico C.
Cunha,Elaine F. F. da
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Santos-Garcia,Letícia
Silva,Daniela R.
Assis,Letícia C.
Assis,Tamiris M. de
Gajo,Giovanna C.
Fernandes,Ítalo Antônio
Ramalho,Teodorico C.
Cunha,Elaine F. F. da
dc.subject.por.fl_str_mv leishmaniasis
inhibitors
4D-QSAR
docking
ADME
topic leishmaniasis
inhibitors
4D-QSAR
docking
ADME
description N-Myristoylation protein is catalyzed by N-myristoyltransferase (NMT), an essential target in Leishmania donovani, the causative agent of kala-azar. Four-dimensional quantitative structure-activity relationship (4D-QSAR) analysis was applied to a series of 77 Leishmania donovani NMT inhibitors. Then, three new compounds were proposed using QSAR models. In addition, molecular docking was performed to predict the binding affinities and interaction modes among the proposed compounds and the NMT active site. In silico absorption, distribution, metabolism and excretion (ADME) evaluation was performed and potential inhibitors demonstrated satisfactory pharmacokinetic properties.
publishDate 2018
dc.date.none.fl_str_mv 2018-07-01
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532018000701440
url http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532018000701440
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 10.21577/0103-5053.20180007
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv text/html
dc.publisher.none.fl_str_mv Sociedade Brasileira de Química
publisher.none.fl_str_mv Sociedade Brasileira de Química
dc.source.none.fl_str_mv Journal of the Brazilian Chemical Society v.29 n.7 2018
reponame:Journal of the Brazilian Chemical Society (Online)
instname:Sociedade Brasileira de Química (SBQ)
instacron:SBQ
instname_str Sociedade Brasileira de Química (SBQ)
instacron_str SBQ
institution SBQ
reponame_str Journal of the Brazilian Chemical Society (Online)
collection Journal of the Brazilian Chemical Society (Online)
repository.name.fl_str_mv Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)
repository.mail.fl_str_mv ||office@jbcs.sbq.org.br
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