In Silico Identification and In Vitro Evaluation of Natural Inhibitors of Leishmania major Pteridine Reductase I.

In a continuation of our computational efforts to find new natural inhibitors of a variety of target enzymes from parasites causing neglected tropical diseases (NTDs), we now report on 15 natural products (NPs) that we have identified as inhibitors of pteridine reductase I (PTR1) through a combination of in silico and in vitro investigations. Pteridine reductase (PTR1) is an enzyme of the trypanosomatid parasites' peculiar folate metabolism, and has previously been validated as a drug target. Initially, pharmacophore queries were created based on four 3D structures of PTR1 using co-crystallized known inhibitors as templates.