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:3.6.1.3 (
ATPase
)
65,361
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Digitoxigenin
alpha-L-, beta-L-, alpha-D-, and beta-D-glucosides; alpha-L-, beta-L-, alpha-D-, and beta-D-mannosides; and alpha-L- and beta-L-rhamnosides were stereoselectively synthesized from the corresponding sugar tetrabenzyl trichloroacetimidates. The Na+,K+-
ATPase
receptor inhibitory activities of these glycosides (as a measure of receptor binding) were compared with those of digitoxigenin, digitoxigenin 6'-hydroxy-beta-D-digitoxoside, digitoxigenin beta-D-galactoside, and digitoxigenin beta-D-digitoxoside. The observed activities reveal that a given sugar substituent may have a role in binding of some glycoside stereoisomers, but not others. With alpha-L- and possibly beta-L-rhamnosides, the 5'-CH3 and 4'-OH appear to have a predominant role in binding to the Na+,K+-
ATPase
receptor. Addition of a 6'-OH to form the corresponding mannosides dramatically disrupts the effect of both the 5'-CH3 and 4'-OH in prompting receptor binding of the alpha-L isomer. However, with the beta-L isomer, some influence of 4'-OH, 3'-OH, and 2'-OH binding remains. With beta-D-glycosides, binding via the "5'-CH3 site" appears to be of little importance and addition of a 6'-OH diminishes activity only slightly. With these beta-D-glycosides, an equatorial 4'-OH, axial 3'-OH, and equatorial 2'-OH groups appear to contribute to binding.
...
PMID:Cardiac glycosides. 7. Sugar stereochemistry and cardiac glycoside activity. 302 Feb 48
In recent years, cardiac glycosides (CGs) have been investigated as potential antiviral and anticancer drugs.
Digitoxigenin
(
DIG
) and other CGs have been shown to bind and inhibit Na
+
/K
+
-
adenosinetriphosphatase
(
ATPase
). Tumor cells show a higher expression rate of the Na
+
/K
+
-
ATPase
protein or a stronger affinity towards the binding of CGs and are therefore more prone to CGs than non-tumor cells. Cancer imaging techniques using radiotracers targeted at specific receptors have yielded successful results. Technetium-99m (
99m
Tc) is one of the radionuclides of choice to radiolabel pharmaceuticals because of its favorable physical and chemical properties along with reasonable costs. Herein, we describe a new Na
+
/K
+
-
ATPase
targeting radiotracer consisting of digitoxigenin and diethylenetriaminepentaacetic acid (DTPA), a bifunctional chelating ligand used to prepare
99m
Tc-labeled complexes, and its evaluation as an imaging probe. We report the synthesis and characterization of the radiolabeled compound including stability tests, blood clearance, and biodistribution in healthy mice. Additionally, we investigated the binding of the compound to A549 human non-small-cell lung cancer cells and the inhibition of the Na
+
/K
+
-
ATPase
by the labeled compound in vitro. The
99m
Tc-labeled DTPA-digitoxigenin (
99m
Tc-DTPA-
DIG
) compound displayed high stability in vitro and in vivo, a fast renal excretion, and a specific binding towards A549 cancer cells in comparison to non-tumor cells. Therefore,
99m
Tc-DTPA-
DIG
could potentially be used for non-invasive visualization of tumor lesions by means of scintigraphic imaging.
...
PMID:New
99m
Tc-Labeled Digitoxigenin Derivative for Cancer Cell Identification. 3189 Oct 85
