Overall, the designed compounds present a useful stepping stone to further optimization as single or dual-PTR1 inhibitors, effective against trypanosomatid parasites. More specifically, for the amide-based inhibitors, such as 1b, one might consider applying a conformational locking strategy to enforce the amide conformation to be more favorable for targeting TbPTR1, and to potentially increase specificity towards PTR1. Furthermore, it might be interesting to explore other potential targets for 1a and 1b, since we expect that additional targets to play a role in their on-parasite activity.