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

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. Here, it was demonstrated that the anthocyanidin delphinidin showed a non-competitive inhibition mechanism of TcAK (Ki arginine = 1.32 mu M and Ki ATP = 500 mu M). Molecular docking simulations predicted that delphinidin occupies part of the ATP/ADP pocket, more specifically the one that binds the ribose phosphate, and molecular dynamics simulations confirmed the amino acids involved in binding. Delphinidin exerted trypanocidal activity over T. cruzi trypomastigotes with a calculated IC50 of 19.51 mu 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.

Automated summary

The study showed that the anthocyanidin delphinidin inhibits the activity of Trypanosoma cruzi arginine kinase with a non-competitive mechanism. Delphinidin was found to exert trypanocidal activity with low toxicity, making it a potential candidate for the development of drugs for Chagas disease treatment.