Molecular docking and binding mode analysis of plant alkaloids as in vitro and in silico inhibitors of trypanothione reductase from trypanosoma cruzi

Alonso J. Argüelles, Geoffrey A. Cordell, Helena Maruenda

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

15 Citas (Scopus)

Resumen

Trypanothione reductase (TryR) is a key enzyme in the metabolism of Trypanosoma cruzi, the parasite responsible for Chagas disease. The available repertoire of TryR inhibitors relies heavily on synthetic substrates of limited structural diversity, and less on plant-derived natural products. In this study, a molecular docking procedure using a Lamarckian Genetic Algorithm was implemented to examine the protein-ligand binding interactions of strong in vitro inhibitors for which no X-ray data is available. In addition, a small, skeletally diverse, set of natural alkaloids was assessed computationally against T. cruzi TryR in search of new scaffolds for lead development. The preferential binding mode (low number of clusters, high cluster population), together with the deduced binding interactions were used to discriminate among the virtual inhibitors. This study confirms the prior in vitro data and proposes quebrachamine, cephalotaxine, cryptolepine, (22S,25S)-tomatidine, (22R,25S)-solanidine, and (22R,25R)-solasodine as new alkaloid scaffold leads in the search for more potent and selective TryR inhibitors.
Idioma originalEspañol
Páginas (desde-hasta)57-62
Número de páginas6
PublicaciónNatural Product Communications
Volumen11
EstadoPublicada - 23 ene. 2016

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