2-4-diaminopteridine and 2-4-diaminoquinazoline

2-4-diaminopteridine has been researched along with 2-4-diaminoquinazoline* in 2 studies

Other Studies

2 other study(ies) available for 2-4-diaminopteridine and 2-4-diaminoquinazoline

ArticleYear
In vitro activities of 2,4-diaminoquinazoline and 2,4-diaminopteridine derivatives against Plasmodium falciparum.
    Antimicrobial agents and chemotherapy, 2004, Volume: 48, Issue:10

    The activities of 28 6-substituted 2,4-diaminoquinazolines, 2,4-diamino-5,6,7,8-tetrahydroquinazolines, and 2,4-diaminopteridines against Plasmodium falciparum were tested. The 50% inhibitory concentrations (IC(50)s) of six compounds were <50 nM, and the most potent compound was 2,4-diamino-5-chloro-6-[N-(2,5-dimethoxybenzyl)amino]quinazoline (compound 1), with an IC(50) of 9 nM. The activity of compound 1 was potentiated by the dihydropteroate synthase inhibitor dapsone, an indication that these compounds are inhibitors of dihydrofolate reductase. Further studies are warranted to assess the therapeutic potential of this combination in vivo.

    Topics: Animals; Antimalarials; Dapsone; Dihydropteroate Synthase; Drug Resistance; Folic Acid Antagonists; Plasmodium falciparum; Pteridines; Quinazolines; Saccharomyces cerevisiae; Tetrahydrofolate Dehydrogenase

2004
Computation of affinity and selectivity: binding of 2,4-diaminopteridine and 2,4-diaminoquinazoline inhibitors to dihydrofolate reductases.
    Journal of computer-aided molecular design, 1998, Volume: 12, Issue:2

    Binding energy calculations for complexes of mutant and wild-type human dihydrofolate reductases with 2,4-diaminopteridine and 2,4-diaminoquinazoline inhibitors are reported. Quantitative insight into binding energetics of these molecules is obtained from calculations based on force field energy evaluation and thermal sampling by molecular dynamics simulations. The calculated affinity of methotrexate for wild-type and mutant enzymes is reasonably well reproduced. Truncation of the methotrexate glutamate tail results in a loss of affinity by several orders of magnitude. No major difference in binding strength is predicted between the pteridines and the quinazolìnes, while the N-methyl group present in methotrexate appears to confer significantly stronger binding. The recent improvement, which is used here, of our linear interaction energy method for binding affinity prediction, as well as problems with treating charged and flexible ligands are discussed. This approach should be suitable in a drug discovery context for prediction of binding energies of new inhibitors prior to their synthesis, when some information about the binding mode is available.

    Topics: Computer Simulation; Drug Design; Folic Acid Antagonists; Humans; Mathematical Computing; Models, Molecular; Protein Binding; Pteridines; Quinazolines; Substrate Specificity; Tetrahydrofolate Dehydrogenase

1998