Anti-Trypanosoma cruzi Properties of Sesquiterpene Lactones Isolated from Stevia spp.: In Vitro and In Silico Studies

BORGO J; ELSO OG; GOMEZ J; COLL M; CATALÁN CAN; MUCCI J; ALVAREZ G; RANDALL LM; BARRERA P; MALCHIODI EL; BIVONA AE; MARTINI MF; SÜLSEN VP

Pharmaceutics

MDPI

Lugar: Basilea; Año: 2023

Stevia species (Asteraceae) have been a rich source of terpenoid compounds, mainly sesquiterpene lactones, several of which show antiprotozoal activity. In the search for new trypanocidal com-pounds, S. satureiifolia var. satureiifolia and S. alpina were studied. Two sesquiterpene lactones, santhemoidin C and 2-oxo-8-deoxyligustrin, respectively were isolated. These compounds were assessed in vitro against Trypanosoma cruzi stages showing IC50 values of 11.80 and 4.98 on epi-mastigotes, 56.08 and 26.19 on trypomastigotes and 4.88 and 20.20 µM on amastigotes, respec-tively. Cytotoxicity was evaluated on Vero cells by the MTT assay. The effect of the compounds on Trypanothyone reductase (TcTR), Trans-sialidase (TcTS) and the prolyl oligopeptidase of 80 kDa (Tc80) as potential molecular targets of T. cruzi was investigated. Santhemoidin C inhibited oli-gopeptidase activity when tested against recombinant Tc80 using a fluorometric assay, reaching an IC50 of 34.9 µM. Molecular docking was performed to study the interaction between santhe-moidin C and the Tc80 protein, reaching high docking energy levels. Plasma membrane shedding and cytoplasmic vacuoles, resembling autophagosomes, were detected by transmission micros-copy in parasites treated with santhemoidin C. Based on these results, santhemoidin C represents a promising candidate for further studies in the search for new molecules for the development of trypanocidal drugs.