One approach to designing new anti-trypanosomatid drugs is to block the folate pathway of trypanosomatids . For the Leishmania species, this requires inhibiting both dihydrofolate reductase (DHFR) and the trypanosomatid-specific enzyme pteridine reductase 1 (PTR1) , whereas for T. brucei, PTR1 (TbPTR1, Fig. ) was shown to be essential for parasite survival and therefore its inhibition alone should be sufficient. Anti-PTR1 drug design campaigns reported to date, including those of the NMTrypI (New Medicines for Trypanosomatidic Infections) consortium () , have resulted in many hits and leads . These include compounds based on the folate substrate and classical inhibitor scaffolds , diverse compounds from virtual screening of compound libraries , and compounds from exploring other scaffolds and from fragment-based drug design (FBDD) approaches .