Effect of capsaicin on the protozoan parasite Trypanosoma cruzi

VALERA-VERA, EDWARD A; REIGADA, CHANTAL; SAYÉ, MELISA; DIGIROLAMO, FABIO A; GALCERAN, FACUNDO; MIRANDA, MARIANA R; PEREIRA, CLAUDIO A

FEMS Microbiology Letters

Oxford University Press

Año: 2020 vol. 367

Trypanosoma cruzi is the causative agent of Chagas disease. There are only two approved treatments, both of themunsuitable for the chronic phase, therefore the development of new drugs is a priority. Trypanosoma cruzi arginine kinase(TcAK) is a promising drug target since it is absent in humans and it is involved in cellular stress responses. In a previousstudy, possible TcAK inhibitors were identified through computer simulations resulting the best compounds capsaicin andcyanidin derivatives. Here, we evaluate the effect of capsaicin on TcAK activity and its trypanocidal effect. Althoughcapsaicin produced a weak enzyme inhibition, it had a strong trypanocidal effect on epimastigotes and trypomastigotes(IC50 = 6.26 μM and 0.26 μM, respectively) being 20-fold more active on trypomastigotes than mammalian cells. Capsaicinwas also active on the intracellular cycle reducing by half the burst of trypomastigotes at approximately 2 μM. Consideringthe difference between the concentrations at which parasite death and TcAK inhibition occur, other possible targets werepredicted.Capsaicin is a selective trypanocidal agent active in nanomolar concentrations, with an IC50 57-fold lower thanbenznidazole, the drug currently used for treating Chagas disease.