Hologram- and descriptor-based QSAR studies for a series of non-azoles derivatives active against C. neoformans
Autor(a) principal: | |
---|---|
Data de Publicação: | 2013 |
Outros Autores: | , |
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=S0103-50532013001000010 |
Resumo: | Over the last decades fungal infections have become an increasing health problem, especially for immunocompromised patients. Unfortunately, the gold standard prophylactic therapy for such ailment is based on azole derivatives, which are fungistatic rather than fungicidal against C. neoformans and cause hepatotoxicity. Aiming at circumvent these problems, non-azole CYP51 inhibitors were designed. Herein a comprehensive structure-activity relationships study was carried out for a dataset of 110 molecules by means of hologram- and descriptor-based QSAR studies. The best descriptor-based QSAR model (r² = 0.92, q² = 0.90, 6 LVs and r²pred =0.86) suggests that resonance effects (ESpm08r) play a major role for antifungal activity. The hologram-based QSAR (r² = 0.87, q² = 0.81, 6 LVs and r²pred = 0.84) supports this hypothesis and hints at steric properties that should also contribute to non-azole inhibitors potency. The insights provided by the integrated analysis of QSAR models, along with their good predictive power prove their usefulness to future drug design efforts. |
id |
SBQ-2_1013010029d63e8bc4473d9a610cccb2 |
---|---|
oai_identifier_str |
oai:scielo:S0103-50532013001000010 |
network_acronym_str |
SBQ-2 |
network_name_str |
Journal of the Brazilian Chemical Society (Online) |
repository_id_str |
|
spelling |
Hologram- and descriptor-based QSAR studies for a series of non-azoles derivatives active against C. neoformansantifungalnon-azolechemometrics2D QSARHQSAROver the last decades fungal infections have become an increasing health problem, especially for immunocompromised patients. Unfortunately, the gold standard prophylactic therapy for such ailment is based on azole derivatives, which are fungistatic rather than fungicidal against C. neoformans and cause hepatotoxicity. Aiming at circumvent these problems, non-azole CYP51 inhibitors were designed. Herein a comprehensive structure-activity relationships study was carried out for a dataset of 110 molecules by means of hologram- and descriptor-based QSAR studies. The best descriptor-based QSAR model (r² = 0.92, q² = 0.90, 6 LVs and r²pred =0.86) suggests that resonance effects (ESpm08r) play a major role for antifungal activity. The hologram-based QSAR (r² = 0.87, q² = 0.81, 6 LVs and r²pred = 0.84) supports this hypothesis and hints at steric properties that should also contribute to non-azole inhibitors potency. The insights provided by the integrated analysis of QSAR models, along with their good predictive power prove their usefulness to future drug design efforts.Sociedade Brasileira de Química2013-10-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532013001000010Journal of the Brazilian Chemical Society v.24 n.10 2013reponame:Journal of the Brazilian Chemical Society (Online)instname:Sociedade Brasileira de Química (SBQ)instacron:SBQ10.5935/0103-5053.20130207info:eu-repo/semantics/openAccessCunha,Lara B.Freitas,Humberto F.Castilho,Marcelo S.eng2015-07-21T00:00:00Zoai:scielo:S0103-50532013001000010Revistahttp://jbcs.sbq.org.brONGhttps://old.scielo.br/oai/scielo-oai.php||office@jbcs.sbq.org.br1678-47900103-5053opendoar:2015-07-21T00:00Journal of the Brazilian Chemical Society (Online) - Sociedade Brasileira de Química (SBQ)false |
dc.title.none.fl_str_mv |
Hologram- and descriptor-based QSAR studies for a series of non-azoles derivatives active against C. neoformans |
title |
Hologram- and descriptor-based QSAR studies for a series of non-azoles derivatives active against C. neoformans |
spellingShingle |
Hologram- and descriptor-based QSAR studies for a series of non-azoles derivatives active against C. neoformans Cunha,Lara B. antifungal non-azole chemometrics 2D QSAR HQSAR |
title_short |
Hologram- and descriptor-based QSAR studies for a series of non-azoles derivatives active against C. neoformans |
title_full |
Hologram- and descriptor-based QSAR studies for a series of non-azoles derivatives active against C. neoformans |
title_fullStr |
Hologram- and descriptor-based QSAR studies for a series of non-azoles derivatives active against C. neoformans |
title_full_unstemmed |
Hologram- and descriptor-based QSAR studies for a series of non-azoles derivatives active against C. neoformans |
title_sort |
Hologram- and descriptor-based QSAR studies for a series of non-azoles derivatives active against C. neoformans |
author |
Cunha,Lara B. |
author_facet |
Cunha,Lara B. Freitas,Humberto F. Castilho,Marcelo S. |
author_role |
author |
author2 |
Freitas,Humberto F. Castilho,Marcelo S. |
author2_role |
author author |
dc.contributor.author.fl_str_mv |
Cunha,Lara B. Freitas,Humberto F. Castilho,Marcelo S. |
dc.subject.por.fl_str_mv |
antifungal non-azole chemometrics 2D QSAR HQSAR |
topic |
antifungal non-azole chemometrics 2D QSAR HQSAR |
description |
Over the last decades fungal infections have become an increasing health problem, especially for immunocompromised patients. Unfortunately, the gold standard prophylactic therapy for such ailment is based on azole derivatives, which are fungistatic rather than fungicidal against C. neoformans and cause hepatotoxicity. Aiming at circumvent these problems, non-azole CYP51 inhibitors were designed. Herein a comprehensive structure-activity relationships study was carried out for a dataset of 110 molecules by means of hologram- and descriptor-based QSAR studies. The best descriptor-based QSAR model (r² = 0.92, q² = 0.90, 6 LVs and r²pred =0.86) suggests that resonance effects (ESpm08r) play a major role for antifungal activity. The hologram-based QSAR (r² = 0.87, q² = 0.81, 6 LVs and r²pred = 0.84) supports this hypothesis and hints at steric properties that should also contribute to non-azole inhibitors potency. The insights provided by the integrated analysis of QSAR models, along with their good predictive power prove their usefulness to future drug design efforts. |
publishDate |
2013 |
dc.date.none.fl_str_mv |
2013-10-01 |
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=S0103-50532013001000010 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S0103-50532013001000010 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.5935/0103-5053.20130207 |
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.24 n.10 2013 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 |
_version_ |
1750318175296159744 |