Pages S2-S9: detailed anti-T.cruzi profile of the early hit benzylMD 4a in the primary screening assays in vitro (Figure ), in the sterile cidality assay (Table , Figure ) and in vivo (Figure ). Pages S10-S13: drug combination with vitamin C (Table ) and preliminary study on the early hit benzylMD 4a for reactive oxygen species (ROS) generation (Figures ). Pages S14-S140: 1 H and 13 C { 1 H} NMR spectra of all new compounds. The total elimination of parasitemia is a key element for the development of new drug candidates during the chronic phase of the disease because of T. cruzi amastigotes ability for recrudescence after drug treatment. The early anti-T. cruzi hit 4a was also tested for sterile cidality and was validated under the conditions for causing no relapse of intra-macrophagic amastigotes after drug wash-out, advocating for delivery of sterile cure in vivo. ). On the other hand, benznidazole and posaconazole displayed no cytotoxicity at the doses tested.