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

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 p...

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Detalles Bibliográficos
Autores principales: 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
Formato: Articulo
Lenguaje:Inglés
Publicado: 2020
Materias:
Biología
Chagas
Carbonic anhydrase
Virtual screening
Sulphamides
Sodium cyclamate
Acesulphame
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/119120
Aporte de:
SEDICI (UNLP) de Universidad Nacional de La Plata
id I19-R120-10915-119120
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Chagas
Carbonic anhydrase
Virtual screening
Sulphamides
Sodium cyclamate
Acesulphame
spellingShingle Biología
Chagas
Carbonic anhydrase
Virtual screening
Sulphamides
Sodium cyclamate
Acesulphame
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
A structure-based approach towards the identification of novel antichagasic compounds: <i>Trypanosoma cruzi</i> carbonic anhydrase inhibitors
topic_facet Biología
Chagas
Carbonic anhydrase
Virtual screening
Sulphamides
Sodium cyclamate
Acesulphame
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.
format Articulo
Articulo
author 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_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_sort Llanos, Manuel Augusto
title A structure-based approach towards the identification of novel antichagasic compounds: <i>Trypanosoma cruzi</i> carbonic anhydrase inhibitors
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 structure-based approach towards the identification of novel antichagasic compounds: <i>trypanosoma cruzi</i> carbonic anhydrase inhibitors
publishDate 2020
url http://sedici.unlp.edu.ar/handle/10915/119120
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