Trypanocidal activity of the anthocyanidin delphinidin, a non-competitive inhibitor of arginine kinase

VALERA VERA E; REIGADA C; MARTÍNEZ SAYÉ M; DI GIROLAMO F; GALCERAN F; MIRANDA MR; PEREIRA CA

NATURAL PRODUCT RESEARCH

TAYLOR & FRANCIS LTD

Lugar: Londres; Año: 2021

1478-6419

Arginine kinase from Trypanosoma cruzi (TcAK) catalyzes the interconversion of arginine andphosphoarginine to maintain the ATP/ADP cell balance, and is involved in the parasites‟ energetichomeostasis and stress responses. Using virtual screening approaches, some plant-derivedpolyphenolic pigments, such as anthocyanidins, were predicted to inhibit TcAK activity. Here, it wasdemonstrated that the anthocyanidin delphinidin showed a non-competitive inhibition mechanism ofTcAK (Ki arginine = 1.32 µM and Ki ATP = 500 µM). Molecular docking simulations predicted thatdelphinidin occupies part of the ATP/ADP pocket, more specifically the one that binds the ribosephosphate, and molecular dynamics simulations confirmed the amino acids involved in binding.Delphinidin exerted trypanocidal activity over T. cruzi trypomastigotes with a calculated IC50 of 19.51µM. Anthocyanidins are low-toxicity natural products which can be exploited for the development oftrypanocidal drugs with less secondary effects than those currently used for the treatment of Chagasdisease.