Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
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Enzyme
Compound
Query: EC:1.2.1.13 (
glyceraldehyde-3-phosphate dehydrogenase
)
6,511
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The effects of K2PtCl4, cis-Pt(
NH3
)2Cl2, and trans-Pt(
NH3
)2Cl2 on the activities of
glyceraldehyde-3-phosphate dehydrogenase
, glucose-6-phosphate dehydrogenase, dihydrofolate reductase, fructose-1,6-bisphosphate aldolase, catalase, tyrosinase, and peroxidase have been investigated. All of the enzymes which are thought to have essential sulfhydryl groups (
glyceraldehyde-3-phosphate dehydrogenase
, aldolase, and glucose-6-phosphate dehydrogenase) were significantly inhibited by K2PtCl4. The other four enzymes studied are not known to have essential sulfhydryl groups, and were not significantly affected by the Pt compounds under the conditions employed. Glyceraldehyde-3-phosphate dehydrogenase was the only enzyme inhibited by all three Pt compounds tested, with K2PtCl4 being the most effective and cis-Pt(
NH3
)2Cl2 the least effective inhibitor. Semilogarithmic plots of residual activity versus inhibition time indicated that the inhibition reactions were not simple first-order processes, except for the inhibition of glucose-6-phosphate dehydrogenase by K2PtCl4 which appeared to be first-order with respect to enzyme concentration.
...
PMID:The effects of platinum complexes on seven enzymes. 11 85
The ruthenium NO donors of the group trans-[Ru(NO)(
NH3
)4L]n+, where the ligand (L) is N-heterocyclic H2O, SO(3)(2-), or triethyl phosphite, are able to lyse Trypanosoma cruzi in vitro and in vivo. Using half-maximal (50%) inhibitory concentrations against bloodstream trypomastigotes (IC50try) and cytotoxicity data on mammalian V-79 cells (IC50V79), the in vitro therapeutic indices (TIs) (IC50V79/IC50try) for these compounds were calculated. Compounds that exhibited an in vitro TI of > or = 10 and trypanocidal activity against both epimastigotes and trypomastigotes with an IC50(try/epi) of < or = 100 microM were assayed in a mouse model for acute Chagas' disease, using two different routes (intraperitoneal and oral) for drug administration. A dose-effect relationship was observed, and from that, the ideal dose of 400 nmol/kg of body weight for both trans-[Ru(NO)(
NH3
)4isn](BF4)3 (isn, isonicotinamide) and trans-[Ru(NO)(
NH3
)4imN](BF4)3 (imN, imidazole) and median (50%) effective doses (ED50) of 86 and 190 nmol/kg, respectively, were then calculated. Since the 50% lethal doses (LD50) for both compounds are higher than 125 micromol/kg, the in vivo TIs (LD50/ED50) of the compounds are 1,453 for trans-[Ru(NO)(
NH3
)4isn](BF4)3 and 658 for trans-[Ru(NO)(
NH3
)4imN](BF4)3. Although these compounds exhibit a marked trypanocidal activity and are able to react with cysteine, they exhibit very low activity in T. cruzi-glycosomal
glyceraldehyde-3-phosphate dehydrogenase
tests, suggesting that this enzyme is not their target. The trans-[Ru(NO)(
NH3
)4isn](BF4)3 and trans-[Ru(NO)(
NH3
)4imN](BF4)3 compounds are able to eliminate amastigote nests in myocardium tissue at 400-nmol/kg doses and ensure the survival of all infected mice, thus opening a novel set of therapies to try against trypanosomatids.
...
PMID:Experimental chemotherapy against Trypanosoma cruzi infection using ruthenium nitric oxide donors. 1958 64
