Genetic studies indicate that the enzyme pteridine reductase 1 (PTR1) is essential for the survival of the protozoan parasite Trypanosoma brucei. Herein, we describe the development and optimisation of a novel series of PTR1 inhibitors, based on benzo[d]imidazol-2-amine derivatives. Data are reported on 33 compounds. This series was initially discovered by a virtual screening campaign (J. Med. ...

The difference spectra associated with complex formation at pH 7.0 between bacteriophage T4-specific dihydrofolate reductase and the 4-amino folate analogues, aminopterin, methotrexate, and N1o-formyl-aminopterin, have features which are similar to the difference spectra obtained for the free compounds in acid versus neutral solutions. These results suggest that oxidized 4-amino-folate compound...

Biopterin is required for growth of the protozoan parasite Leishmania and is salvaged from the host through the activities of a novel biopterin transporter (BT1) and broad-spectrum pteridine reductase (PTR1). Here we characterize Leishmania major quinonoid-dihydropteridine reductase (LmQDPR), the key enzyme required for regeneration and maintenance of H(4)biopterin pools. LmQDPR shows good homo...

The Synthesis and Characterization of Ru(bpy)2(L-pteridine) and Ru(phen)2(L-pteridine) complexes Ruthenium (II) polypyridyl complexes are very important biochemical compounds because of their interactions with DNA. In this study, these complexes are analyzed to understand how their physical properties, chemical properties, and interactions with DNA are affected by structural differences of the ...

Pteridine reductase 1 (PTR1) is an NADPH dependent reductase that catalyzes the reduction of several pterins and folates. The gene encoding this enzyme was originally identified in Leishmania based on its abilty to provide resistance to the drug methotrexate (MTX). The DNA and amno acid sequences are known , and overproducing strains of Escherichia coli are available. PTR1 has been previously s...

Pteridine reductase (PTR1) is an NADPH-dependent short-chain reductase found in parasitic trypanosomatid protozoans. The enzyme participates in the salvage of pterins and represents a target for the development of improved therapies for infections caused by these parasites. A series of crystallographic analyses of Leishmania major PTR1 are reported. Structures of the enzyme in a binary complex ...

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 Leishmania major pteridine reductase I (LmPTR1) through a combination of in silico and in vitro investigations. Pteridine reductase (PTR1) is an ...