Hundreds of millions of people worldwide are affected by Chagas’ disease caused by
Trypanosoma cruzi. Since the current treatment lack efficacy, specificity, and suffers from several side-effects, novel therapeutics are mandatory. Natural products from endophytic fungi have been useful sources of lead compounds. In this study, three lactones isolated from an endophytic strain culture were
in silico evaluated for rational guidance of their bioassay screening. All lactones displayed
in vitro activity against
T. cruzi epimastigote and trypomastigote forms. Notably, the IC
50 values of (+)-phomolactone were lower than benznidazole (0.86 vs. 30.78 μM against epimastigotes and 0.41 vs. 4.88 μM against trypomastigotes). Target-based studies suggested that lactones displayed their trypanocidal activities due to
T. cruzi glyceraldehyde-3-phosphate dehydrogenase (
TcGAPDH) inhibition, and the binding free energy for all three
TcGAPDH-lactone complexes suggested that (+)-phomolactone has a lower score value (−3.38), corroborating with IC
50 assays. These results highlight the potential of these lactones for further anti-
T. cruzi drug development.
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