INVESTIGADORES
CARRILLO carolina
artículos
Título:
A Structure-Based Approach Towards the Identification of Novel Antichagasic Compounds. Trypanosoma cruzi Carbonic Anhydrase Inhibitors
Autor/es:
LLANOS MA; SBARAGLINI ML; VILLALBA ML; RUIZ MD; CARRILLO C; ALBA SOTO CD; TALEVI A; ANGELI A; PARKKILA S; SUPURAN CT; GAVERNET L
Revista:
Journal of Enzyme Inhibition and Medicinal Chemistry
Editorial:
Taylor & Francis
Referencias:
Año: 2019 vol. 35 p. 21 - 30
ISSN:
1475-6374
Resumen:
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 modeling, 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 strongly selective for TcCA over human carbonic anhydrase (CAII isoform), which is encouraging in terms of the therapeutic safety and efficacy.