In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues

Autores
Michelini, Flavia Mariana; Ramirez, Javier Alberto; Berra, Alejandro; Galagovsky, Lydia Raquel; Alche, Laura Edith
Año de publicación
2004
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Brassinosteroids are a novel group of steroids that appear to be ubiquitous in plants and are essential for normal plant growth and development. It has been previously reported that brassinosteroid analogues exert an antiviral activity against herpes simplex virus type 1 (HSV-1) and arenaviruses. In the present study, we report the chemical synthesis of compounds (22S,23S)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one (2), (22S,23S)-5α-fluoro-3β-22,23-trihydroxystigmastan-6-one (3), (22S,23S)-3β,5α,22,23-tetrahydroxy-stigmastan-6-one (4) as well as their antiherpetic activity both in a human conjunctive cell line (IOBA-NHC) and in the murine herpetic stromal keratitis (HSK) experimental model. All compounds prevented HSV-1 multiplication in NHC cells in a dose dependent manner when added after infection with no cytotoxicity. Administration of compounds 2, 3, and 4 to the eyes of mice at 1, 2, and 3 days post-infection delayed and reduced the incidence of HSK, consisting mainly of inflammation, vascularization, and necrosis, compared to untreated, infected mice. However, viral titers of eye washes showed no differences among samples from treated and untreated mice. Since the decrease in the percentage of mice with ocular lesions occurred 5 days after treatment had ended, we suggest that brassinosteroids 2, 3, and 4 did not exert a direct antiviral effect in vivo, but rather may play a role in immune-mediated stromal inflammation, which would explain the improvement of the clinical signs of HSK observed.
Fil: Michelini, Flavia Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina
Fil: Ramirez, Javier Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina
Fil: Berra, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Galagovsky, Lydia Raquel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina
Fil: Alche, Laura Edith. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina
Materia
ANTIVIRAL ACTIVITY
BRASSINOSTEROIDS
HSV-1
HUMAN CONJUNCTIVE CELL LINE
MURINE HERPETIC STROMAL KERATITIS
STEROID
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:11336/99096
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/99096
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analoguesMichelini, Flavia MarianaRamirez, Javier AlbertoBerra, AlejandroGalagovsky, Lydia RaquelAlche, Laura EdithANTIVIRAL ACTIVITYBRASSINOSTEROIDSHSV-1HUMAN CONJUNCTIVE CELL LINEMURINE HERPETIC STROMAL KERATITISSTEROIDhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Brassinosteroids are a novel group of steroids that appear to be ubiquitous in plants and are essential for normal plant growth and development. It has been previously reported that brassinosteroid analogues exert an antiviral activity against herpes simplex virus type 1 (HSV-1) and arenaviruses. In the present study, we report the chemical synthesis of compounds (22S,23S)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one (2), (22S,23S)-5α-fluoro-3β-22,23-trihydroxystigmastan-6-one (3), (22S,23S)-3β,5α,22,23-tetrahydroxy-stigmastan-6-one (4) as well as their antiherpetic activity both in a human conjunctive cell line (IOBA-NHC) and in the murine herpetic stromal keratitis (HSK) experimental model. All compounds prevented HSV-1 multiplication in NHC cells in a dose dependent manner when added after infection with no cytotoxicity. Administration of compounds 2, 3, and 4 to the eyes of mice at 1, 2, and 3 days post-infection delayed and reduced the incidence of HSK, consisting mainly of inflammation, vascularization, and necrosis, compared to untreated, infected mice. However, viral titers of eye washes showed no differences among samples from treated and untreated mice. Since the decrease in the percentage of mice with ocular lesions occurred 5 days after treatment had ended, we suggest that brassinosteroids 2, 3, and 4 did not exert a direct antiviral effect in vivo, but rather may play a role in immune-mediated stromal inflammation, which would explain the improvement of the clinical signs of HSK observed.Fil: Michelini, Flavia Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; ArgentinaFil: Ramirez, Javier Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Berra, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; ArgentinaFil: Galagovsky, Lydia Raquel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; ArgentinaFil: Alche, Laura Edith. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; ArgentinaElsevier Science Inc2004-10info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/99096Michelini, Flavia Mariana; Ramirez, Javier Alberto; Berra, Alejandro; Galagovsky, Lydia Raquel; Alche, Laura Edith; In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues; Elsevier Science Inc; Steroids; 69; 11-12; 10-2004; 713-7200039-128XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.sciencedirect.com/science/article/pii/S0039128X04001412info:eu-repo/semantics/altIdentifier/doi/10.1016/j.steroids.2004.04.011info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:06:24Zoai:ri.conicet.gov.ar:11336/99096instacron: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:34982025-09-10 13:06:24.86CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues
title In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues
spellingShingle In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues
Michelini, Flavia Mariana
ANTIVIRAL ACTIVITY
BRASSINOSTEROIDS
HSV-1
HUMAN CONJUNCTIVE CELL LINE
MURINE HERPETIC STROMAL KERATITIS
STEROID
title_short In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues
title_full In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues
title_fullStr In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues
title_full_unstemmed In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues
title_sort In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues
dc.creator.none.fl_str_mv Michelini, Flavia Mariana
Ramirez, Javier Alberto
Berra, Alejandro
Galagovsky, Lydia Raquel
Alche, Laura Edith
author Michelini, Flavia Mariana
author_facet Michelini, Flavia Mariana
Ramirez, Javier Alberto
Berra, Alejandro
Galagovsky, Lydia Raquel
Alche, Laura Edith
author_role author
author2 Ramirez, Javier Alberto
Berra, Alejandro
Galagovsky, Lydia Raquel
Alche, Laura Edith
author2_role author
author
author
author
dc.subject.none.fl_str_mv ANTIVIRAL ACTIVITY
BRASSINOSTEROIDS
HSV-1
HUMAN CONJUNCTIVE CELL LINE
MURINE HERPETIC STROMAL KERATITIS
STEROID
topic ANTIVIRAL ACTIVITY
BRASSINOSTEROIDS
HSV-1
HUMAN CONJUNCTIVE CELL LINE
MURINE HERPETIC STROMAL KERATITIS
STEROID
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Brassinosteroids are a novel group of steroids that appear to be ubiquitous in plants and are essential for normal plant growth and development. It has been previously reported that brassinosteroid analogues exert an antiviral activity against herpes simplex virus type 1 (HSV-1) and arenaviruses. In the present study, we report the chemical synthesis of compounds (22S,23S)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one (2), (22S,23S)-5α-fluoro-3β-22,23-trihydroxystigmastan-6-one (3), (22S,23S)-3β,5α,22,23-tetrahydroxy-stigmastan-6-one (4) as well as their antiherpetic activity both in a human conjunctive cell line (IOBA-NHC) and in the murine herpetic stromal keratitis (HSK) experimental model. All compounds prevented HSV-1 multiplication in NHC cells in a dose dependent manner when added after infection with no cytotoxicity. Administration of compounds 2, 3, and 4 to the eyes of mice at 1, 2, and 3 days post-infection delayed and reduced the incidence of HSK, consisting mainly of inflammation, vascularization, and necrosis, compared to untreated, infected mice. However, viral titers of eye washes showed no differences among samples from treated and untreated mice. Since the decrease in the percentage of mice with ocular lesions occurred 5 days after treatment had ended, we suggest that brassinosteroids 2, 3, and 4 did not exert a direct antiviral effect in vivo, but rather may play a role in immune-mediated stromal inflammation, which would explain the improvement of the clinical signs of HSK observed.
Fil: Michelini, Flavia Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina
Fil: Ramirez, Javier Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina
Fil: Berra, Alejandro. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Medicina; Argentina
Fil: Galagovsky, Lydia Raquel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Orgánica; Argentina
Fil: Alche, Laura Edith. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Química Biológica; Argentina
description Brassinosteroids are a novel group of steroids that appear to be ubiquitous in plants and are essential for normal plant growth and development. It has been previously reported that brassinosteroid analogues exert an antiviral activity against herpes simplex virus type 1 (HSV-1) and arenaviruses. In the present study, we report the chemical synthesis of compounds (22S,23S)-3β-bromo-5α,22,23-trihydroxystigmastan-6-one (2), (22S,23S)-5α-fluoro-3β-22,23-trihydroxystigmastan-6-one (3), (22S,23S)-3β,5α,22,23-tetrahydroxy-stigmastan-6-one (4) as well as their antiherpetic activity both in a human conjunctive cell line (IOBA-NHC) and in the murine herpetic stromal keratitis (HSK) experimental model. All compounds prevented HSV-1 multiplication in NHC cells in a dose dependent manner when added after infection with no cytotoxicity. Administration of compounds 2, 3, and 4 to the eyes of mice at 1, 2, and 3 days post-infection delayed and reduced the incidence of HSK, consisting mainly of inflammation, vascularization, and necrosis, compared to untreated, infected mice. However, viral titers of eye washes showed no differences among samples from treated and untreated mice. Since the decrease in the percentage of mice with ocular lesions occurred 5 days after treatment had ended, we suggest that brassinosteroids 2, 3, and 4 did not exert a direct antiviral effect in vivo, but rather may play a role in immune-mediated stromal inflammation, which would explain the improvement of the clinical signs of HSK observed.
publishDate 2004
dc.date.none.fl_str_mv 2004-10
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/99096
Michelini, Flavia Mariana; Ramirez, Javier Alberto; Berra, Alejandro; Galagovsky, Lydia Raquel; Alche, Laura Edith; In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues; Elsevier Science Inc; Steroids; 69; 11-12; 10-2004; 713-720
0039-128X
CONICET Digital
CONICET
url http://hdl.handle.net/11336/99096
identifier_str_mv Michelini, Flavia Mariana; Ramirez, Javier Alberto; Berra, Alejandro; Galagovsky, Lydia Raquel; Alche, Laura Edith; In vitro and in vivo antiherpetic activity of three new synthetic brassinosteroid analogues; Elsevier Science Inc; Steroids; 69; 11-12; 10-2004; 713-720
0039-128X
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://www.sciencedirect.com/science/article/pii/S0039128X04001412
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.steroids.2004.04.011
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
application/pdf
application/pdf
application/pdf
application/pdf
dc.publisher.none.fl_str_mv Elsevier Science Inc
publisher.none.fl_str_mv Elsevier Science Inc
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
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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