There is a need for improved and generally applicable scoring functions for fragment-based approaches to ligand design. Here, we evaluate the performance of a computationally efficient model for inhibitory activity estimation, which is composed only of multipole electrostatic energy and dispersion energy terms that approximate long-range ab initio quantum mechanical interaction energies. We fin...

A great number of sesquiterpenes are reported in the available literature as good antileishmanial leads. However, their mode of action at the molecular level has not been elucidated. The lack of molecular studies could be considered an impediment for studies seeking to improve sesquiterpene-based drug design. The present in silico study allows us to make important observations about the molecul...

The apparent structural similarity between purines and pteridines has been the subject of a number of studies attempting to demonstrate a relationship between these compounds in living systems. That a relationship does, in fact, exist has been shown, not only by purine incorporation into a pteridine (l-3), but also by the ability of at least one organism (Alcaligines fuecalis) to degrade a pter...

It is shown that an enzyme from Colias butterflies, oxidizing the yellow pteridine xanthopterin to the colorless pteridine leucopterin, is in fact xanthine dehydrogenase. Methods for the partial purification of the enzyme are given. The enzyme oxidizes a number of purines and pteridines effectively, with NAD+ as cosubstrate. It is inhibited competitively by its products of reaction, leucopterin...

Pteridine reductase (PTR1) is a potential target for drug development against parasitic Trypanosoma and Leishmania species, protozoa that are responsible for a range of serious diseases found in tropical and subtropical parts of the world. As part of a structure-based approach to inhibitor development, specifically targeting Leishmania species, well ordered crystals of L. donovani PTR1 were sou...

Ciliapterin, a new unconjugated pteridine, has been isolated from the ciliated protozoan, Tefrahymena pyriformis. It has been determined by alkaline permanganate oxidation to be a 2-amino-4-hydroxy-6-substituted pteridine and by acid hydrolytic treatment to possess no labile bonds (such as glycosidic or phosphoester). The substitution at position 6 is dihydroxypropyl, as shown by the identifica...

Trypanosomatid parasitic protozoans of the genus Leishmania are autotrophic for both folate and unconjugated pteridines. Leishmania salvage these metabolites from their mammalian hosts and insect vectors through multiple transporters. Within the parasite, folates are reduced by a bifunctional DHFR (dihydrofolate reductase)-TS (thymidylate synthase) and by a novel PTR1 (pteridine reductase 1), w...

We have tested the hypothesis that 2,4-diamino-6-hydroxymethyl-pteridine (DAP), 2,4-diaminopteroic acid (DAPA), and 2,4 diamino-N10-methyl-pteroic acid (DAMPA) could be converted into aminopterin (from DAP and DAPA) and methotrexate (from DAMPA), both of which are potent inhibitors of dihydrofolate reductase, a proven drug target for Plasmodium falciparum. DAP, DAPA, and DAMPA inhibited parasit...