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)
Starting from 4,4'-diamino-diphenylsulfone (DDS) as a lead structure, new 2-substituted analogues as well as new 2-substituted 4-alkylamino-4'-amino diphenylsulfones have been designed and synthetized in different ways. This has led to compounds the inhibitory activity of which against 7,8-dihydropteroic acid synthase of plasmodia and mycobacteria is clearly superior to that of sulfadoxine and in most cases to that of DDS. Of special interest is 4'-amino-4-n-propylamino-2-methyl-diphenylsulfone. Together with inhibitors of
7,8-dihydrofolate reductase
in vitro and in vivo it possesses a marked synergistic inhibitory activity against plasmodia. In contrast to DDS in doses up to 200 mg/kg p.o. (cat) no
methemoglobin
formation is observed. The compound has been selected for further studies.
...
PMID:Preparation and biological activity of new substituted antimalarial diaminodiphenylsulfones. 268 56
New diaminodiphenylsulfone inhibitors of dihydropteroate synthase are described with increased inhibitory activity against mycobacteria and plasmodia, whereas their side effect of
methemoglobin
formation could be suppressed. The optimization of diaminobenzylpyrimidines, inhibitors of
dihydrofolate reductase
, led to derivatives with increased inhibitory effect against mycobacteria, especially M. leprae and plasmodia. Some of these derivatives show autosynergism. Finally the combination of brodimoprim (BDP) and dapsone (DDS) was developed for the treatment of leprosy. First clinical trials in Paraguay and Ethiopia show that combinations of BDP/DDS and BDP/DDS plus rifampicin were highly effective and may become an alternative multi-drug therapy for the treatment of leprosy. The tolerance of the regimens used was generally good.
...
PMID:In vitro and in vivo results of brodimoprim and analogues alone and in combination against E. coli and mycobacteria. 819 33
