Virtual screening of flavonoids as possible inhibitors of Trypanosoma cruzi arginine kinase

VALERA-VERA, EDWARD; REIGADA, CHANTAL; SAYE, MELISA; MIRANDA, MARIANA; PEREIRA, CA

CABA

Congreso; XXIX Reunión Anual de la Sociedad Argentina de Protozoología (SAP); 2017

Sociedad Argentina de Protozoología (SAP)

Arginine kinase from Trypanosoma cruzi (TcAK) is an enzyme involvedin the energetic homeostasis and response to stressors inthe parasite. The activity of enzyme, among some of its homologuesfrom diverse phyla, is inhibited by some flavonoid compounds. Inaddition to it, one of these inhibitors, the resveratrol, affected thereplication and survival of cultured epimastigotes as well as amastigotes/trypomastigotes infecting mammal cell cultures. In order totest other molecules that can throw light on the mode of interactionbetween the enzyme and the flavonoids, we arranged a simplepipeline that narrows the focus of the testing efforts to a handful ofcompounds.For this, we downloaded the (now unavailable) database of medicallyactive plant substances (MAPS), specifically the subset offlavonoid molecules, that comprised 326 compounds, and modeledthe molecular interactions between these flavonoids and a homologymodel of TcAK obtained from the iTASSER online server. Thesemodels were carried on two different molecular docking softwares,the open source AutoDock Vina, and the private licensed OpenEye.Results from each software were ordered according to its dockingscore, and then both lists were compared to take only the moleculesthat were present between the best 100 scores of both programs,from which only 5 where shared among the first 20, 7 among thefirst 50 and 29 among e first 100. From these molecules, only 7are purchasable, and three of them (delphinidine, malvidine andpetunidine) were also present as possibly active compounds in theprevious virtual screening that pointed out resveratrol as an inhibitorof the TcAK activity, making them of high interest for future in-vitrotests.