Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:1.5.1.3 (
dihydrofolate reductase
)
5,819
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
2-Amino-4-(3,5-diacetylphenyl)amino-1,6-dimethylpyrimidinium chloride (
CNI
-H0294) is a novel arylene bis(methylketone) compound that displays antimalarial activity against chloroquine- and pyrimethamine-resistant Plasmodium falciparum clones. The compound has been found to be concentrated into infected erythrocytes, with 80-179 microM accumulated when parasites were cultured in the presence of 1.0 microM
CNI
-H0294. Uninfected erythrocytes, in contrast, only accumulated 2.5-3.4 microM
CNI
-H0294 under identical conditions. Using postmitochondrial supernatants from a number of parasite clones, the compound was found to inhibit
dihydrofolate reductase
(
EC 1.5.1.3
) activity with an IC50 of 243-483 microM. Thus, while
CNI
-H0294 is not a powerful inhibitor of plasmodial
dihydrofolate reductase
, the accumulation of the compound into infected erythrocytes, when correlated to the external ED50 concentration against parasite growth in vitro, reaches concentrations sufficient to inhibit the malarial enzyme.
...
PMID:Studies on the mechanism of antimalarial action of a novel arylene bis(methylketone). 931 Mar 51
