Inhibition of lanosterol 14 alpha-demethylase: Molecular modeling study of triazole derivatives acting against the phytopathogen Botrytis cinerea

Autores
Parravicini, Oscar; Andujar, Sebastian Antonio
Año de publicación
2021
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Botrytis cinerea is a phytopathogenic fungus that causes the gray mold disease. It isconsidered a main factor in post-harvest losses in fresh fruit crops, causing seriouseconomic losses in the agricultural industry. In addition, it has become an importantmodel for the molecular study of necrotrophic fungi. Although there are fungicides for itscontrol, many of them have failed since B. cinerea has evolved a variety of infectionmechanisms due to its genetic variability. In this regard, triazoles have been used for thecontrol of several pathogenic fungi. These compounds act as inhibitor of the lanosterol14 alpha-demethylase, a cytochrome p450 (CYP54B)-dependent enzyme systeminvolved in the synthesis of ergosterol.In order to explain the biological behavior of different CYP54B-triazole complexes weperformed a combined molecular modeling study. In this way, we determined theconformational aspects of the currently available triazole antifungal agents whencomplexed with CYP54B. Furthermore, a new series of novel triazole derivatives wassynthesized and their inhibitory activity was assessed. Some of them showed stronginhibitory effects comparable to that observed for commercial antifungal drugs. Themolecular modeling study was carried out in three stages. First, we conducted moleculardocking calculations. Next, we performed molecular dynamics (MD) simulations and freeenergy of the different complexes was calculated. Finally, we performed a per-residueanalysis in order to identify the amino acids involved in the intermolecular interactions ofthe complexes.Our molecular modeling study indicated that all active compounds are bounded in asimilar spatial arrangement. Thus, it is reasonable to assume that the compoundsstudied here interact with the same region of the enzyme. MD simulations enable us toexplain the different activities displayed by these compounds. The main stabilizinginteractions are Tyr101, Thr105, Tyr115, Phe208, Ala287, His290 and Ile353.
Fil: Parravicini, Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Andujar, Sebastian Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
XLVIV Reunión Anual de la Sociedad de Biofísica. Biofísica en tiempos de COVID-19.
Ciudad Autónoma de Buenos Aires
Argentina
Sociedad Argentina de Biofísica
Materia
14 alpha-demethylase
Molecular modeling
triazole derivatives
phytopathogen Botrytis cinerea
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/247650
Acceder
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repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Inhibition of lanosterol 14 alpha-demethylase: Molecular modeling study of triazole derivatives acting against the phytopathogen Botrytis cinereaParravicini, OscarAndujar, Sebastian Antonio14 alpha-demethylaseMolecular modelingtriazole derivativesphytopathogen Botrytis cinereahttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Botrytis cinerea is a phytopathogenic fungus that causes the gray mold disease. It isconsidered a main factor in post-harvest losses in fresh fruit crops, causing seriouseconomic losses in the agricultural industry. In addition, it has become an importantmodel for the molecular study of necrotrophic fungi. Although there are fungicides for itscontrol, many of them have failed since B. cinerea has evolved a variety of infectionmechanisms due to its genetic variability. In this regard, triazoles have been used for thecontrol of several pathogenic fungi. These compounds act as inhibitor of the lanosterol14 alpha-demethylase, a cytochrome p450 (CYP54B)-dependent enzyme systeminvolved in the synthesis of ergosterol.In order to explain the biological behavior of different CYP54B-triazole complexes weperformed a combined molecular modeling study. In this way, we determined theconformational aspects of the currently available triazole antifungal agents whencomplexed with CYP54B. Furthermore, a new series of novel triazole derivatives wassynthesized and their inhibitory activity was assessed. Some of them showed stronginhibitory effects comparable to that observed for commercial antifungal drugs. Themolecular modeling study was carried out in three stages. First, we conducted moleculardocking calculations. Next, we performed molecular dynamics (MD) simulations and freeenergy of the different complexes was calculated. Finally, we performed a per-residueanalysis in order to identify the amino acids involved in the intermolecular interactions ofthe complexes.Our molecular modeling study indicated that all active compounds are bounded in asimilar spatial arrangement. Thus, it is reasonable to assume that the compoundsstudied here interact with the same region of the enzyme. MD simulations enable us toexplain the different activities displayed by these compounds. The main stabilizinginteractions are Tyr101, Thr105, Tyr115, Phe208, Ala287, His290 and Ile353.Fil: Parravicini, Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaFil: Andujar, Sebastian Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; ArgentinaXLVIV Reunión Anual de la Sociedad de Biofísica. Biofísica en tiempos de COVID-19.Ciudad Autónoma de Buenos AiresArgentinaSociedad Argentina de BiofísicaSociedad Argentina de Biofísica2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectCongresoBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/247650Inhibition of lanosterol 14 alpha-demethylase: Molecular modeling study of triazole derivatives acting against the phytopathogen Botrytis cinerea; XLVIV Reunión Anual de la Sociedad de Biofísica. Biofísica en tiempos de COVID-19.; Ciudad Autónoma de Buenos Aires; Argentina; 2021; 73-73CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/publicaciones/libros-de-resumenes/Nacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:35:46Zoai:ri.conicet.gov.ar:11336/247650instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:35:47.08CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Inhibition of lanosterol 14 alpha-demethylase: Molecular modeling study of triazole derivatives acting against the phytopathogen Botrytis cinerea
title Inhibition of lanosterol 14 alpha-demethylase: Molecular modeling study of triazole derivatives acting against the phytopathogen Botrytis cinerea
spellingShingle Inhibition of lanosterol 14 alpha-demethylase: Molecular modeling study of triazole derivatives acting against the phytopathogen Botrytis cinerea
Parravicini, Oscar
14 alpha-demethylase
Molecular modeling
triazole derivatives
phytopathogen Botrytis cinerea
title_short Inhibition of lanosterol 14 alpha-demethylase: Molecular modeling study of triazole derivatives acting against the phytopathogen Botrytis cinerea
title_full Inhibition of lanosterol 14 alpha-demethylase: Molecular modeling study of triazole derivatives acting against the phytopathogen Botrytis cinerea
title_fullStr Inhibition of lanosterol 14 alpha-demethylase: Molecular modeling study of triazole derivatives acting against the phytopathogen Botrytis cinerea
title_full_unstemmed Inhibition of lanosterol 14 alpha-demethylase: Molecular modeling study of triazole derivatives acting against the phytopathogen Botrytis cinerea
title_sort Inhibition of lanosterol 14 alpha-demethylase: Molecular modeling study of triazole derivatives acting against the phytopathogen Botrytis cinerea
dc.creator.none.fl_str_mv Parravicini, Oscar
Andujar, Sebastian Antonio
author Parravicini, Oscar
author_facet Parravicini, Oscar
Andujar, Sebastian Antonio
author_role author
author2 Andujar, Sebastian Antonio
author2_role author
dc.subject.none.fl_str_mv 14 alpha-demethylase
Molecular modeling
triazole derivatives
phytopathogen Botrytis cinerea
topic 14 alpha-demethylase
Molecular modeling
triazole derivatives
phytopathogen Botrytis cinerea
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Botrytis cinerea is a phytopathogenic fungus that causes the gray mold disease. It isconsidered a main factor in post-harvest losses in fresh fruit crops, causing seriouseconomic losses in the agricultural industry. In addition, it has become an importantmodel for the molecular study of necrotrophic fungi. Although there are fungicides for itscontrol, many of them have failed since B. cinerea has evolved a variety of infectionmechanisms due to its genetic variability. In this regard, triazoles have been used for thecontrol of several pathogenic fungi. These compounds act as inhibitor of the lanosterol14 alpha-demethylase, a cytochrome p450 (CYP54B)-dependent enzyme systeminvolved in the synthesis of ergosterol.In order to explain the biological behavior of different CYP54B-triazole complexes weperformed a combined molecular modeling study. In this way, we determined theconformational aspects of the currently available triazole antifungal agents whencomplexed with CYP54B. Furthermore, a new series of novel triazole derivatives wassynthesized and their inhibitory activity was assessed. Some of them showed stronginhibitory effects comparable to that observed for commercial antifungal drugs. Themolecular modeling study was carried out in three stages. First, we conducted moleculardocking calculations. Next, we performed molecular dynamics (MD) simulations and freeenergy of the different complexes was calculated. Finally, we performed a per-residueanalysis in order to identify the amino acids involved in the intermolecular interactions ofthe complexes.Our molecular modeling study indicated that all active compounds are bounded in asimilar spatial arrangement. Thus, it is reasonable to assume that the compoundsstudied here interact with the same region of the enzyme. MD simulations enable us toexplain the different activities displayed by these compounds. The main stabilizinginteractions are Tyr101, Thr105, Tyr115, Phe208, Ala287, His290 and Ile353.
Fil: Parravicini, Oscar. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
Fil: Andujar, Sebastian Antonio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina
XLVIV Reunión Anual de la Sociedad de Biofísica. Biofísica en tiempos de COVID-19.
Ciudad Autónoma de Buenos Aires
Argentina
Sociedad Argentina de Biofísica
description Botrytis cinerea is a phytopathogenic fungus that causes the gray mold disease. It isconsidered a main factor in post-harvest losses in fresh fruit crops, causing seriouseconomic losses in the agricultural industry. In addition, it has become an importantmodel for the molecular study of necrotrophic fungi. Although there are fungicides for itscontrol, many of them have failed since B. cinerea has evolved a variety of infectionmechanisms due to its genetic variability. In this regard, triazoles have been used for thecontrol of several pathogenic fungi. These compounds act as inhibitor of the lanosterol14 alpha-demethylase, a cytochrome p450 (CYP54B)-dependent enzyme systeminvolved in the synthesis of ergosterol.In order to explain the biological behavior of different CYP54B-triazole complexes weperformed a combined molecular modeling study. In this way, we determined theconformational aspects of the currently available triazole antifungal agents whencomplexed with CYP54B. Furthermore, a new series of novel triazole derivatives wassynthesized and their inhibitory activity was assessed. Some of them showed stronginhibitory effects comparable to that observed for commercial antifungal drugs. Themolecular modeling study was carried out in three stages. First, we conducted moleculardocking calculations. Next, we performed molecular dynamics (MD) simulations and freeenergy of the different complexes was calculated. Finally, we performed a per-residueanalysis in order to identify the amino acids involved in the intermolecular interactions ofthe complexes.Our molecular modeling study indicated that all active compounds are bounded in asimilar spatial arrangement. Thus, it is reasonable to assume that the compoundsstudied here interact with the same region of the enzyme. MD simulations enable us toexplain the different activities displayed by these compounds. The main stabilizinginteractions are Tyr101, Thr105, Tyr115, Phe208, Ala287, His290 and Ile353.
publishDate 2021
dc.date.none.fl_str_mv 2021
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
Congreso
Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/247650
Inhibition of lanosterol 14 alpha-demethylase: Molecular modeling study of triazole derivatives acting against the phytopathogen Botrytis cinerea; XLVIV Reunión Anual de la Sociedad de Biofísica. Biofísica en tiempos de COVID-19.; Ciudad Autónoma de Buenos Aires; Argentina; 2021; 73-73
CONICET Digital
CONICET
url http://hdl.handle.net/11336/247650
identifier_str_mv Inhibition of lanosterol 14 alpha-demethylase: Molecular modeling study of triazole derivatives acting against the phytopathogen Botrytis cinerea; XLVIV Reunión Anual de la Sociedad de Biofísica. Biofísica en tiempos de COVID-19.; Ciudad Autónoma de Buenos Aires; Argentina; 2021; 73-73
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/url/https://biofisica.org.ar/publicaciones/libros-de-resumenes/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
application/pdf
dc.coverage.none.fl_str_mv Nacional
dc.publisher.none.fl_str_mv Sociedad Argentina de Biofísica
publisher.none.fl_str_mv Sociedad Argentina de Biofísica
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
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repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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