A Structure-Based Approach Towards the Identification of Novel Antichagasic Compounds. Trypanosoma cruzi Carbonic Anhydrase Inhibitors

SBARAGLINI, MARÍA L.; CARRILLO, CAROLINA; ANGELI, ANDREA; GAVERNET, LUCIANA; LLANOS, MANUEL A.; RUIZ, MARÍA D.; TALEVI, ALAN; SUPURAN, CLAUDIU T.; VILLALBA, MARÍA L.; SOTO, CATALINA ALBA; PARKKILA, SEPPO

Journal of Enzyme Inhibition and Medicinal Chemistry

Taylor & Francis

Lugar: Londres; Año: 2020 vol. 35 p. 21 - 30

1475-6374

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.