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

The enzyme arginine kinase from Trypanosoma cruzi (TcAK) catalyzes the interconversion of arginine and phosphoarginine to maintain the ATP/ADP cell balance, and is involved in the parasites energetic homeostasis and stress responses. Using virtual screening approaches, some plant-derived polyphenolic pigments such as anthocyanidins, were predicted to inhibit TcAK activity. In this work, it was demonstrated that the anthocyanidin delphinidin showed a non-competitive inhibition mechanism of TcAK in vitro (Ki arginine = 1.32 M and Ki ATP = 500 M). Molecular docking simulations predicted that delphinidin occupies a hydrophobic pocket close to the ATP/ADP binding site. Delphinidin also exerted trypanocidal activity over T. cruzi trypomastigotes with a calculated IC50 of 19.51 M. Anthocyanidins are low-toxicity natural products which can be exploited for the development of trypanocidal drugs with less secondary effects than those currently used for the treatment of Chagas disease.