The treatment of Human African trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important; pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp., has been identified as a candidate target, and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 fr...

background : leishmaniasis is an endemic disease in 88 countries. reports on leishmania drug resistance are growing in number. the mechanism of unresponsiveness against glucantime in iranian cutaneous leishmaniasis has not yet been characterized. to begin the first step in finding an anti- leishmania chemotherapy, we prepared recombinant l. major ptr1 enzyme and characterized its activity by en...

Pistacia integerrima Stew ex Brandis is a valued medicinal plant used for curing various diseases such as diarrhea, fever, liver disorder, pain, asthma, and inflammation. The aim of this study was the isolation bioactive leishmanicidal agents from methanolic extract. extract led to flavonoids 3,5,7,4/-tetrahydroxy-flavanone (1). isolated compound 1 were tested antileishmanial effect. showed per...

Keywords: DHFR-inhibiting activity, pteridine, furo[3,2-g]pteridine, molecular docking, QSAR-analysis

Pteridine reductase 1 (PTR1) is a novel broad spectrum enzyme of pterin and folate metabolism in the protozoan parasite Leishmania. Overexpression of PTR1 confers methotrexate resistance to these protozoa, arising from the enzyme's ability to reduce dihydrofolate and its relative insensitivity to methotrexate. The kinetic mechanism and stereochemical course for the catalyzed reaction confirm PT...

The enzyme pteridine reductase (PTR1) has recently been discovered in the protozoan parasite Leishmania and validated as a target for therapeutic intervention. PTR1 is responsible for the salvage of pteridines and also contributes to antifolate drug resistance. Structural analysis, in combination with ongoing biochemical characterization will assist the elucidation of the structure-activity rel...

BACKGROUND Currently, there are no effective vaccines against leishmaniasis, and treatment using pentavalent antimonial drugs is occasionally effective and often toxic for patients. The PTR1 enzyme, which causes antifolate drug resistance in Leishmania parasites encoded by gene pteridine reductase 1 (ptr1). Since Leishmania lacks pteridine and folate metabolism, it cannot synthesize the pteridi...