VIRTUAL SCREENING OF FLAVONOIDS AS POSSIBLE INHIBITORS OF TRYPANOSOMA CRUZI ARGININE KINASE

VALERA VERA E; REIGADA C; MARTÍNEZ SAYÉ M; MIRANDA MR; PEREIRA CA

Congreso; Reunión Conjunta de Sociedades de Biociencias (XXIX Reunión de la Sociedad Argentina de Protozoología); 2017

Sociedad Argentina de Protozoología

Arginine kinase from Trypanosoma cruzi (TcAK) is an enzyme involved in the energetic homeostasis and response to stressors in the parasite. The activity of enzyme, among some of its homologues from diverse phyla, is inhibited by some flavonoid compounds. In addition to it, one of these inhibitors, the resveratrol, affected the replication 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 interaction between the enzyme and the flavonoids, we arranged a simple pipeline that narrows the focus of the testing efforts to a handful of compounds.For this, we downloaded the (now unavailable) database of medically active plant substances (MAPS), specifically the subset of flavonoid molecules, that comprised 326 compounds, and modeled the molecular interactions between these flavonoids and a homology model of TcAK obtained from the iTASSER online server. These models 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 docking score, and then both lists were compared to take only the molecules that were present between the best 100 scores of both programs, from which only 5 where shared among the first 20, 7 among the first 50 and 29 among e first 100. From these molecules, only 7are purchasable, and three of them (delphinidine, malvidine and petunidine) were also present as possibly active compounds in the previous virtual screening that pointed out resveratrol as an inhibitor of the TcAK activity, making them of high interest for future in-vitro tests.