Anti-Parasitic drugsDiscovery of potent pteridine reductase inhibitors to guide antiparasite drug development.

Inhibition of pteridine reductase (PTR1) — an enzyme essential for parasitic trypanosomatid survival — might represent a therapeutic approach for African sleeping sickness. Cavazzuti and colleagues combined a rapid-screening strategy using a folate-based library with structure-based design to identify PTR1 inhibitors with biological activity. An additive profile was observed when PTR1 inhibitors were used in combination with known dihydrofolate reductase inhibitors, indicating the potential of targeting two enzymes for the development of previously undescribed antiparasitic drugs.