Stereoselective Activity of 1-Propargyl-4-styrylpiperidine-like Analogues That Can Discriminate between Monoamine Oxidase Isoforms A and B

Autores
Knez, Damijan; Colettis, Natalia Claudia; Iacovino, Luca G.; Sova, Matej; Pišlar, Anja; Konc, Janez; Lešnik, Samo; Higgs, Josefina; Kamecki González, Fabiola Elizabeth; Mangialavori, Irene Cecilia; Dolšak, Ana; Žakelj, Simon; Trontelj, Jurij; Kos, Janko; Binda, Claudia; Marder, Nora Mariel; Gobec, Stanislav
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
The resurgence of interest in monoamine oxidases (MAOs) has been fueled by recent correlations of this enzymatic activity with cardiovascular, neurological, and oncological disorders. This has promoted increased research into selective MAO-A and MAO-B inhibitors. Here, we shed light on how selective inhibition of MAO-A and MAO-B can be achieved by geometric isomers of cis-and trans-1-propargyl-4-styrylpiperidines. While the cis isomers are potent human MAO-A inhibitors, the trans analogues selectively target only the MAO-B isoform. The inhibition was studied by kinetic analysis, UV-vis spectrum measurements, and X-ray crystallography. The selective inhibition of the MAO-A and MAO-B isoforms was confirmed ex vivo in mouse brain homogenates, and additional in vivo studies in mice show the therapeutic potential of 1-propargyl-4-styrylpiperidines for central nervous system disorders. This study represents a unique case of stereoselective activity of cis/trans isomers that can discriminate between structurally related enzyme isoforms.
Fil: Knez, Damijan. University of Ljubljana; Eslovenia
Fil: Colettis, Natalia Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Iacovino, Luca G.. Universita Degli Studi Di Pavia; Italia
Fil: Sova, Matej. University of Ljubljana; Eslovenia
Fil: Pišlar, Anja. University of Ljubljana; Eslovenia
Fil: Konc, Janez. National Institute of Chemistry; Eslovenia
Fil: Lešnik, Samo. National Institute of Chemistry; Eslovenia
Fil: Higgs, Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Kamecki González, Fabiola Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Mangialavori, Irene Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Dolšak, Ana. University of Ljubljana; Eslovenia
Fil: Žakelj, Simon. University of Ljubljana; Eslovenia
Fil: Trontelj, Jurij. University of Ljubljana; Eslovenia
Fil: Kos, Janko. University of Ljubljana; Eslovenia
Fil: Binda, Claudia. Universita Degli Studi Di Pavia; Italia
Fil: Marder, Nora Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Gobec, Stanislav. University of Ljubljana; Eslovenia
Materia
Compuestos sinteticos
Inhibidores MAO
actividad estereoselectiva
Sistema Nervioso Central
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/149074
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Stereoselective Activity of 1-Propargyl-4-styrylpiperidine-like Analogues That Can Discriminate between Monoamine Oxidase Isoforms A and BKnez, DamijanColettis, Natalia ClaudiaIacovino, Luca G.Sova, MatejPišlar, AnjaKonc, JanezLešnik, SamoHiggs, JosefinaKamecki González, Fabiola ElizabethMangialavori, Irene CeciliaDolšak, AnaŽakelj, SimonTrontelj, JurijKos, JankoBinda, ClaudiaMarder, Nora MarielGobec, StanislavCompuestos sinteticosInhibidores MAOactividad estereoselectivaSistema Nervioso Centralhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1The resurgence of interest in monoamine oxidases (MAOs) has been fueled by recent correlations of this enzymatic activity with cardiovascular, neurological, and oncological disorders. This has promoted increased research into selective MAO-A and MAO-B inhibitors. Here, we shed light on how selective inhibition of MAO-A and MAO-B can be achieved by geometric isomers of cis-and trans-1-propargyl-4-styrylpiperidines. While the cis isomers are potent human MAO-A inhibitors, the trans analogues selectively target only the MAO-B isoform. The inhibition was studied by kinetic analysis, UV-vis spectrum measurements, and X-ray crystallography. The selective inhibition of the MAO-A and MAO-B isoforms was confirmed ex vivo in mouse brain homogenates, and additional in vivo studies in mice show the therapeutic potential of 1-propargyl-4-styrylpiperidines for central nervous system disorders. This study represents a unique case of stereoselective activity of cis/trans isomers that can discriminate between structurally related enzyme isoforms.Fil: Knez, Damijan. University of Ljubljana; EsloveniaFil: Colettis, Natalia Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Iacovino, Luca G.. Universita Degli Studi Di Pavia; ItaliaFil: Sova, Matej. University of Ljubljana; EsloveniaFil: Pišlar, Anja. University of Ljubljana; EsloveniaFil: Konc, Janez. National Institute of Chemistry; EsloveniaFil: Lešnik, Samo. National Institute of Chemistry; EsloveniaFil: Higgs, Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Kamecki González, Fabiola Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Mangialavori, Irene Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Dolšak, Ana. University of Ljubljana; EsloveniaFil: Žakelj, Simon. University of Ljubljana; EsloveniaFil: Trontelj, Jurij. University of Ljubljana; EsloveniaFil: Kos, Janko. University of Ljubljana; EsloveniaFil: Binda, Claudia. Universita Degli Studi Di Pavia; ItaliaFil: Marder, Nora Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; ArgentinaFil: Gobec, Stanislav. University of Ljubljana; EsloveniaAmerican Chemical Society2020-01info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/149074Knez, Damijan; Colettis, Natalia Claudia; Iacovino, Luca G.; Sova, Matej; Pišlar, Anja; et al.; Stereoselective Activity of 1-Propargyl-4-styrylpiperidine-like Analogues That Can Discriminate between Monoamine Oxidase Isoforms A and B; American Chemical Society; Journal of Medicinal Chemistry; 63; 3; 1-2020; 1361-13870022-2623CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.9b01886info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jmedchem.9b01886info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-11-12T09:53:28Zoai:ri.conicet.gov.ar:11336/149074instacron: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:34982025-11-12 09:53:28.598CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Stereoselective Activity of 1-Propargyl-4-styrylpiperidine-like Analogues That Can Discriminate between Monoamine Oxidase Isoforms A and B
title Stereoselective Activity of 1-Propargyl-4-styrylpiperidine-like Analogues That Can Discriminate between Monoamine Oxidase Isoforms A and B
spellingShingle Stereoselective Activity of 1-Propargyl-4-styrylpiperidine-like Analogues That Can Discriminate between Monoamine Oxidase Isoforms A and B
Knez, Damijan
Compuestos sinteticos
Inhibidores MAO
actividad estereoselectiva
Sistema Nervioso Central
title_short Stereoselective Activity of 1-Propargyl-4-styrylpiperidine-like Analogues That Can Discriminate between Monoamine Oxidase Isoforms A and B
title_full Stereoselective Activity of 1-Propargyl-4-styrylpiperidine-like Analogues That Can Discriminate between Monoamine Oxidase Isoforms A and B
title_fullStr Stereoselective Activity of 1-Propargyl-4-styrylpiperidine-like Analogues That Can Discriminate between Monoamine Oxidase Isoforms A and B
title_full_unstemmed Stereoselective Activity of 1-Propargyl-4-styrylpiperidine-like Analogues That Can Discriminate between Monoamine Oxidase Isoforms A and B
title_sort Stereoselective Activity of 1-Propargyl-4-styrylpiperidine-like Analogues That Can Discriminate between Monoamine Oxidase Isoforms A and B
dc.creator.none.fl_str_mv Knez, Damijan
Colettis, Natalia Claudia
Iacovino, Luca G.
Sova, Matej
Pišlar, Anja
Konc, Janez
Lešnik, Samo
Higgs, Josefina
Kamecki González, Fabiola Elizabeth
Mangialavori, Irene Cecilia
Dolšak, Ana
Žakelj, Simon
Trontelj, Jurij
Kos, Janko
Binda, Claudia
Marder, Nora Mariel
Gobec, Stanislav
author Knez, Damijan
author_facet Knez, Damijan
Colettis, Natalia Claudia
Iacovino, Luca G.
Sova, Matej
Pišlar, Anja
Konc, Janez
Lešnik, Samo
Higgs, Josefina
Kamecki González, Fabiola Elizabeth
Mangialavori, Irene Cecilia
Dolšak, Ana
Žakelj, Simon
Trontelj, Jurij
Kos, Janko
Binda, Claudia
Marder, Nora Mariel
Gobec, Stanislav
author_role author
author2 Colettis, Natalia Claudia
Iacovino, Luca G.
Sova, Matej
Pišlar, Anja
Konc, Janez
Lešnik, Samo
Higgs, Josefina
Kamecki González, Fabiola Elizabeth
Mangialavori, Irene Cecilia
Dolšak, Ana
Žakelj, Simon
Trontelj, Jurij
Kos, Janko
Binda, Claudia
Marder, Nora Mariel
Gobec, Stanislav
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Compuestos sinteticos
Inhibidores MAO
actividad estereoselectiva
Sistema Nervioso Central
topic Compuestos sinteticos
Inhibidores MAO
actividad estereoselectiva
Sistema Nervioso Central
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv The resurgence of interest in monoamine oxidases (MAOs) has been fueled by recent correlations of this enzymatic activity with cardiovascular, neurological, and oncological disorders. This has promoted increased research into selective MAO-A and MAO-B inhibitors. Here, we shed light on how selective inhibition of MAO-A and MAO-B can be achieved by geometric isomers of cis-and trans-1-propargyl-4-styrylpiperidines. While the cis isomers are potent human MAO-A inhibitors, the trans analogues selectively target only the MAO-B isoform. The inhibition was studied by kinetic analysis, UV-vis spectrum measurements, and X-ray crystallography. The selective inhibition of the MAO-A and MAO-B isoforms was confirmed ex vivo in mouse brain homogenates, and additional in vivo studies in mice show the therapeutic potential of 1-propargyl-4-styrylpiperidines for central nervous system disorders. This study represents a unique case of stereoselective activity of cis/trans isomers that can discriminate between structurally related enzyme isoforms.
Fil: Knez, Damijan. University of Ljubljana; Eslovenia
Fil: Colettis, Natalia Claudia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Iacovino, Luca G.. Universita Degli Studi Di Pavia; Italia
Fil: Sova, Matej. University of Ljubljana; Eslovenia
Fil: Pišlar, Anja. University of Ljubljana; Eslovenia
Fil: Konc, Janez. National Institute of Chemistry; Eslovenia
Fil: Lešnik, Samo. National Institute of Chemistry; Eslovenia
Fil: Higgs, Josefina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Kamecki González, Fabiola Elizabeth. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Mangialavori, Irene Cecilia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Dolšak, Ana. University of Ljubljana; Eslovenia
Fil: Žakelj, Simon. University of Ljubljana; Eslovenia
Fil: Trontelj, Jurij. University of Ljubljana; Eslovenia
Fil: Kos, Janko. University of Ljubljana; Eslovenia
Fil: Binda, Claudia. Universita Degli Studi Di Pavia; Italia
Fil: Marder, Nora Mariel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Química y Físico-Química Biológicas "Prof. Alejandro C. Paladini". Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Química y Físico-Química Biológicas; Argentina
Fil: Gobec, Stanislav. University of Ljubljana; Eslovenia
description The resurgence of interest in monoamine oxidases (MAOs) has been fueled by recent correlations of this enzymatic activity with cardiovascular, neurological, and oncological disorders. This has promoted increased research into selective MAO-A and MAO-B inhibitors. Here, we shed light on how selective inhibition of MAO-A and MAO-B can be achieved by geometric isomers of cis-and trans-1-propargyl-4-styrylpiperidines. While the cis isomers are potent human MAO-A inhibitors, the trans analogues selectively target only the MAO-B isoform. The inhibition was studied by kinetic analysis, UV-vis spectrum measurements, and X-ray crystallography. The selective inhibition of the MAO-A and MAO-B isoforms was confirmed ex vivo in mouse brain homogenates, and additional in vivo studies in mice show the therapeutic potential of 1-propargyl-4-styrylpiperidines for central nervous system disorders. This study represents a unique case of stereoselective activity of cis/trans isomers that can discriminate between structurally related enzyme isoforms.
publishDate 2020
dc.date.none.fl_str_mv 2020-01
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/11336/149074
Knez, Damijan; Colettis, Natalia Claudia; Iacovino, Luca G.; Sova, Matej; Pišlar, Anja; et al.; Stereoselective Activity of 1-Propargyl-4-styrylpiperidine-like Analogues That Can Discriminate between Monoamine Oxidase Isoforms A and B; American Chemical Society; Journal of Medicinal Chemistry; 63; 3; 1-2020; 1361-1387
0022-2623
CONICET Digital
CONICET
url http://hdl.handle.net/11336/149074
identifier_str_mv Knez, Damijan; Colettis, Natalia Claudia; Iacovino, Luca G.; Sova, Matej; Pišlar, Anja; et al.; Stereoselective Activity of 1-Propargyl-4-styrylpiperidine-like Analogues That Can Discriminate between Monoamine Oxidase Isoforms A and B; American Chemical Society; Journal of Medicinal Chemistry; 63; 3; 1-2020; 1361-1387
0022-2623
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://pubs.acs.org/doi/abs/10.1021/acs.jmedchem.9b01886
info:eu-repo/semantics/altIdentifier/doi/10.1021/acs.jmedchem.9b01886
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
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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score 12.976206

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