In T. cruzi epimastigotes, rotenone has been observed to have a weak effect on NADH-fumarate reductase, NADH-cytochrome c reductase, succinate-cytochrome c reductase, and sn-glycerol-phosphate cytochrome c reductase . In addition, T. cruzi kDNA mutants with deletions in complex I subunits demonstrated no changes in mitochondrial bioenergetics, production of ROS, or redox state when compared to their wild-type counterparts, implying a restricted role for complex I in the functioning of T. cruzi epimastigotes . However, no studies have been performed on the amastigote form of the parasite to our knowledge; therefore, the role of complex I in the metabolism of this form remains unclear. The very selective anti-T. cruzi activity observed for compounds 37 to 39, known complex I inhibitors, compared to that of the large set of analogs tested, suggests that the observed activity may be linked to complex I inhibition. However, because of the phenotypic nature of the assay used, we can not exclude that the activity observed is due to action on one or more different target(s). Further target deconvolution experiments are needed to confirm the target identity. structural analysis, the strategy enables fast deconvolution of the compounds responsible for the bioactivity of the crude extracts. This method allows for identification of metabolites responsible for bioactivity in individual extracts, and in the entire NE library, thanks to the connection possible through ENPKG and its multimodal alignment . As showcased in this study, and since plants often produce various structurally related scaffolds, the compounds obtained can be used for structure-activity relationship evaluation. This workflow demonstrates how modern NP research methods can facilitate the transition from an NE library to a digitalized NP library. Together with recent advances in computational metabolomics and data analysis, these advances show how these tools can allow researchers to efficiently explore the potential for natural products drug discovery.