A structure-based approach towards the identification of novel antichagasic compounds: <i>Trypanosoma cruzi</i> carbonic anhydrase inhibitors

Autores
Llanos, Manuel Augusto; Sbaraglini, María Laura; Villalba, María Luisa; Ruiz, María Dolores; Carrillo, Carolina; Soto, Catalina Alba; Talevi, Alan; Angeli, Andrea; Parkkila, Seppo; Supuran, Claudiu T.; Gavernet, Luciana
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Trypanosoma cruzi carbonic anhydrase (TcCA) has recently emerged as an interesting target for the design of new compounds to treat Chagas disease. In this study we report the results of a structure-based virtual screening campaign to identify novel and selective TcCA inhibitors. The combination of properly validated computational methodologies such as comparative modelling, molecular dynamics and docking simulations allowed us to find high potency hits, with KI values in the nanomolar range. The compounds also showed trypanocidal effects against T. cruzi epimastigotes and trypomastigotes. All the candidates are selective for inhibiting TcCA over the human isoform CA II, which is encouraging in terms of possible therapeutic safety and efficacy.
Laboratorio de Investigación y Desarrollo de Bioactivos
Materia
Biología
Chagas
Carbonic anhydrase
Virtual screening
Sulphamides
Sodium cyclamate
Acesulphame
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/119120
Acceder
id SEDICI_1428ef6fea5cd6fd140fae317b2f1871
oai_identifier_str oai:sedici.unlp.edu.ar:10915/119120
network_acronym_str SEDICI
repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling A structure-based approach towards the identification of novel antichagasic compounds: <i>Trypanosoma cruzi</i> carbonic anhydrase inhibitorsLlanos, Manuel AugustoSbaraglini, María LauraVillalba, María LuisaRuiz, María DoloresCarrillo, CarolinaSoto, Catalina AlbaTalevi, AlanAngeli, AndreaParkkila, SeppoSupuran, Claudiu T.Gavernet, LucianaBiologíaChagasCarbonic anhydraseVirtual screeningSulphamidesSodium cyclamateAcesulphameTrypanosoma cruzi carbonic anhydrase (TcCA) has recently emerged as an interesting target for the design of new compounds to treat Chagas disease. In this study we report the results of a structure-based virtual screening campaign to identify novel and selective TcCA inhibitors. The combination of properly validated computational methodologies such as comparative modelling, molecular dynamics and docking simulations allowed us to find high potency hits, with KI values in the nanomolar range. The compounds also showed trypanocidal effects against T. cruzi epimastigotes and trypomastigotes. All the candidates are selective for inhibiting TcCA over the human isoform CA II, which is encouraging in terms of possible therapeutic safety and efficacy.Laboratorio de Investigación y Desarrollo de Bioactivos2020info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf21-30http://sedici.unlp.edu.ar/handle/10915/119120enginfo:eu-repo/semantics/altIdentifier/issn/1475-6366info:eu-repo/semantics/altIdentifier/issn/1475-6374info:eu-repo/semantics/altIdentifier/doi/10.1080/14756366.2019.1677638info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:28:04Zoai:sedici.unlp.edu.ar:10915/119120Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:28:05.05SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv A structure-based approach towards the identification of novel antichagasic compounds: <i>Trypanosoma cruzi</i> carbonic anhydrase inhibitors
title A structure-based approach towards the identification of novel antichagasic compounds: <i>Trypanosoma cruzi</i> carbonic anhydrase inhibitors
spellingShingle A structure-based approach towards the identification of novel antichagasic compounds: <i>Trypanosoma cruzi</i> carbonic anhydrase inhibitors
Llanos, Manuel Augusto
Biología
Chagas
Carbonic anhydrase
Virtual screening
Sulphamides
Sodium cyclamate
Acesulphame
title_short A structure-based approach towards the identification of novel antichagasic compounds: <i>Trypanosoma cruzi</i> carbonic anhydrase inhibitors
title_full A structure-based approach towards the identification of novel antichagasic compounds: <i>Trypanosoma cruzi</i> carbonic anhydrase inhibitors
title_fullStr A structure-based approach towards the identification of novel antichagasic compounds: <i>Trypanosoma cruzi</i> carbonic anhydrase inhibitors
title_full_unstemmed A structure-based approach towards the identification of novel antichagasic compounds: <i>Trypanosoma cruzi</i> carbonic anhydrase inhibitors
title_sort A structure-based approach towards the identification of novel antichagasic compounds: <i>Trypanosoma cruzi</i> carbonic anhydrase inhibitors
dc.creator.none.fl_str_mv Llanos, Manuel Augusto
Sbaraglini, María Laura
Villalba, María Luisa
Ruiz, María Dolores
Carrillo, Carolina
Soto, Catalina Alba
Talevi, Alan
Angeli, Andrea
Parkkila, Seppo
Supuran, Claudiu T.
Gavernet, Luciana
author Llanos, Manuel Augusto
author_facet Llanos, Manuel Augusto
Sbaraglini, María Laura
Villalba, María Luisa
Ruiz, María Dolores
Carrillo, Carolina
Soto, Catalina Alba
Talevi, Alan
Angeli, Andrea
Parkkila, Seppo
Supuran, Claudiu T.
Gavernet, Luciana
author_role author
author2 Sbaraglini, María Laura
Villalba, María Luisa
Ruiz, María Dolores
Carrillo, Carolina
Soto, Catalina Alba
Talevi, Alan
Angeli, Andrea
Parkkila, Seppo
Supuran, Claudiu T.
Gavernet, Luciana
author2_role author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Biología
Chagas
Carbonic anhydrase
Virtual screening
Sulphamides
Sodium cyclamate
Acesulphame
topic Biología
Chagas
Carbonic anhydrase
Virtual screening
Sulphamides
Sodium cyclamate
Acesulphame
dc.description.none.fl_txt_mv Trypanosoma cruzi carbonic anhydrase (TcCA) has recently emerged as an interesting target for the design of new compounds to treat Chagas disease. In this study we report the results of a structure-based virtual screening campaign to identify novel and selective TcCA inhibitors. The combination of properly validated computational methodologies such as comparative modelling, molecular dynamics and docking simulations allowed us to find high potency hits, with KI values in the nanomolar range. The compounds also showed trypanocidal effects against T. cruzi epimastigotes and trypomastigotes. All the candidates are selective for inhibiting TcCA over the human isoform CA II, which is encouraging in terms of possible therapeutic safety and efficacy.
Laboratorio de Investigación y Desarrollo de Bioactivos
description Trypanosoma cruzi carbonic anhydrase (TcCA) has recently emerged as an interesting target for the design of new compounds to treat Chagas disease. In this study we report the results of a structure-based virtual screening campaign to identify novel and selective TcCA inhibitors. The combination of properly validated computational methodologies such as comparative modelling, molecular dynamics and docking simulations allowed us to find high potency hits, with KI values in the nanomolar range. The compounds also showed trypanocidal effects against T. cruzi epimastigotes and trypomastigotes. All the candidates are selective for inhibiting TcCA over the human isoform CA II, which is encouraging in terms of possible therapeutic safety and efficacy.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
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://sedici.unlp.edu.ar/handle/10915/119120
url http://sedici.unlp.edu.ar/handle/10915/119120
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/1475-6366
info:eu-repo/semantics/altIdentifier/issn/1475-6374
info:eu-repo/semantics/altIdentifier/doi/10.1080/14756366.2019.1677638
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by/4.0/
Creative Commons Attribution 4.0 International (CC BY 4.0)
dc.format.none.fl_str_mv application/pdf
21-30
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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score 13.070432

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