2004
DOI: 10.1016/j.bbrc.2004.01.101
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Effect on ribonucleotide reductase of novel lipophilic iron chelators: the desferri-exochelins

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Cited by 28 publications
(22 citation statements)
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“…Deferoxamine is a hexadentate iron chelator that forms a 1:1 ligand metal complex that chelates extracellular iron. 50,51 However, the extracellular iron chelator deferoxamine was significantly less active than CPX in our assays, probably because of the ability of CPX to penetrate through cell membranes and bind intracellular iron. Of note, resistance to CPX was not simply the result of failure of the drug to enter cells or bind iron.…”
Section: Discussionmentioning
confidence: 83%
See 1 more Smart Citation
“…Deferoxamine is a hexadentate iron chelator that forms a 1:1 ligand metal complex that chelates extracellular iron. 50,51 However, the extracellular iron chelator deferoxamine was significantly less active than CPX in our assays, probably because of the ability of CPX to penetrate through cell membranes and bind intracellular iron. Of note, resistance to CPX was not simply the result of failure of the drug to enter cells or bind iron.…”
Section: Discussionmentioning
confidence: 83%
“…by guest www.bloodjournal.org From chelators inhibit ribonucleotide reductase through a different mechanism as they prevent the incorporation of iron into the RRM2 center, thereby inhibiting formation of the tyrosyl radical. 51 We demonstrated that CPX inhibited the activity of ribonucleotide reductase. However, CPX probably also affects other ironcontaining enzymes.…”
Section: Discussionmentioning
confidence: 83%
“…However, in addition to HO-1 there are many other iron regulatory pathways (ferritin) and non-iron pathways (cell replication) that Ngal may stimulate by delivering iron. For example, iron is necessary for the R2 subunit of ribonuclease reductase, the enzyme that synthesizes DNA (89); it enhances the expression of many cyclin genes (90) and stress-related proteins (91); and it inhibits apoptosis mediated by p38 MAPK phosphorylation (92) and NIP3 (93). Last, it is even possible that enterochelin:Fe or its degradation products may scavenge free radicals.…”
Section: Discussionmentioning
confidence: 99%
“…Alternatively, these ligands can interact directly with the hydrophobic iron center of RR (Hodges et al, 2004). Previous evidence has demonstrated an increase in antiproliferative activity with the elevation in chelator hydrophobicity (Johnson et al, 1982;Baker et al, 1985;Hodges et al, 2004).…”
Section: A Antiproliferative Activity and Lipophilicitymentioning
confidence: 99%
“…Alternatively, these ligands can interact directly with the hydrophobic iron center of RR (Hodges et al, 2004). Previous evidence has demonstrated an increase in antiproliferative activity with the elevation in chelator hydrophobicity (Johnson et al, 1982;Baker et al, 1985;Hodges et al, 2004). This trend is attributed to the ability of lipophilic ligands to pass through membranes and thus gain access to intracellular iron pools critical for cellular proliferation (Baker et al, 1985;.…”
Section: A Antiproliferative Activity and Lipophilicitymentioning
confidence: 99%