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bioRxiv · 10.1101/2020.06.23.167452

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

Valera-Vera, E.·Reigada, C.·Saye, M.·Digirolamo, F. A.·Galceran, F.·Miranda, M. R.·Pereira, C. A.
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Abstract

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.

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Valera-Vera, E., Reigada, C., Saye, M., Digirolamo, F. A., Galceran, F., Miranda, M. R., Pereira, C. A.. 2020-06-23. Trypanocidal activity of the anthocyanidin delphinidin, a non-competitive inhibitor of arginine kinase. https://doi.org/10.1101/2020.06.23.167452

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