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
Descripción
Sumario: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.

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