Iron is critical for cell growth and proliferation. Iron chelators are being explored for a number of clinical applications, including the treatment of neurodegenerative disorders, heart disease, and cancer. To uncover mechanisms of action of tachpyridine, a chelator currently undergoing preclinical evaluation as an anticancer agent, cell-cycle analysis was performed. Tachpyridine arrested cell...

PURPOSE The objective of this study was to determine the efficacy of dietary supplementation with the metal chelators, trientine or citric acid, in preventing the development of cardiomyopathy in the Zucker diabetic rat. HYPOTHESIS We hypothesized that dietary chelators would attenuate metal-catalyzed oxidative stress and damage in tissues and protect against pathological changes in ventricul...

Aroylhydrazone and thiosemicarbazone iron (Fe) chelators have potent antitumor activity. The aim of the current study was to examine the antitumor effects and mechanisms of action of a novel series of Fe chelators, the di-2-pyridyl thiosemicarbazones. Of 7 new chelators synthesized, 4 showed pronounced antiproliferative effects. The most active chelator was Dp44mT, which had marked and selectiv...

A purified and electrophoretically homogeneous blue laccase from the litter-decaying basidiomycete Stropharia rugosoannulata with a molecular mass of approximately 66 kDa oxidized Mn to Mn , as assessed in the presence of the Mn chelators oxalate, malonate, and pyrophosphate. At rate-saturating concentrations (100 mM) of these chelators and at pH 5.0, Mn complexes were produced at 0.15, 0.05, a...

Chelators such as 2-hydroxy-1-napthylaldehyde isonicotinoyl hydrazone (311) and di-2-pyridylketone-4,4-dimethyl-3-thiosemicarbazone (Dp44mT) target tumor cell iron pools and inhibit proliferation. These agents also modulate multiple targets, one of which is the cyclin-dependent kinase inhibitor, p21. Hence, this investigation examined the mechanism of action of these compounds in targeting p21....

Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is abundant in plasma and is potentially capable of degrading the anchor utilized by many cell surface proteins. The goal of this work was to study structural features of the GPI-PLD that might be involved in regulation of its activity. Trypsin cleaved the 100-110 kDa GPI-PLD polypeptide into three major fragments (two of approxima...

Agents that modulate cellular iron availability have been studied for their antitumor activity. Based on encouraging in vitro studies, the iron chelator deferoxamine (DFO) has been used in clinical studies to treat cancer patients. The observation that DFO induced macular edema in several cancer patients led to the present investigation of vascular endothelial growth factor (VEGF) as a possible...

Several efforts have been made to detoxify the effect of metals once they are administered in the human body. Chelation is considered the best method used so far. Medicinal treatment of acute and chronic metal toxicity is provided by chelating agents. Chelation is one of the chemical functions that take place in the bodies of almost all living organisms. It is a process by which plants and anim...

Agents that modulate cellular iron availability have been studied for their antitumor activity. Based on encouraging in vitro studies, the iron chelator deferoxamine (DFO) has been used in clinical studies to treat cancer patients. The observation that DFO induced macular edema in several cancer patients led to the present investigation of vascular endothelial growth factor (VEGF) as a possible...

Affibody molecules constitute a class of small (7 kDa) scaffold proteins that can be engineered to have excellent tumor targeting properties. High reabsorption in kidneys complicates development of affibody molecules for radionuclide therapy. In this study, we evaluated the influence of the composition of cysteine-containing C-terminal peptide-based chelators on the biodistribution and renal re...