Disease relevance of Desferrithiocin

• To determine whether this drug might be useful not only for iron-overload but also for immunosuppression, we studied the in vitro effects of desferrithiocin on T-lymphocyte function [1].
• The stereochemistry at C-4 is shown to have a substantial effect on the iron clearing efficiency of desferrithiocin analogues, as does C-4'-hydroxylation on the toxicity profile [2].
• Desferrithiocin, a novel microbial siderophore isolated from cultures of Streptomyces antibioticus DSM 1865, and a number of its derivatives and analogues are evaluated for their ability to promote iron clearance [3].
• Prevention of acetic acid-induced colitis by desferrithiocin analogs in a rat model [4].

High impact information on Desferrithiocin

• Third, the H2O2 scavenger, catalase, and the iron chelators, 1,10-phenanthroline and desferrithiocin, decreased both .OH detection and strand breaks in DNA mixtures exposed to cigarette smoke and asbestos [5].
• A comparative study of the iron-clearing properties of desferrithiocin analogues with desferrioxamine B in a Cebus monkey model [6].
• Although desferrithiocin inhibited the induction of cytotoxic T lymphocyte (CTL) activity, it did not inhibit CTL- or natural killer-induced cytotoxicity [1].
• Desferrithiocin also inhibited proliferation of constitutively dividing, and factor-independent EBV-transformed B cell and leukemic T-cell lines [1].
• Evaluations both in vitro and in vivo were carried out to determine whether there is any advantage, at the level of prevention of Fenton chemistry, radical trapping, or iron clearance, to constructing a desferrithiocin-based hexacoordinate analogue [7].

Biological context of Desferrithiocin

• Effects of C-4 stereochemistry and C-4' hydroxylation on the iron clearing efficiency and toxicity of desferrithiocin analogues [2].
• Pharmacokinetics of orally administered desferrithiocin analogs in cebus apella primates [8].
• Studies in vitro have evaluated the structure-activity relationships and mechanism of action of many classes of iron chelators, including desferrioxamine (DFO), pyridoxal isonicotinoyl hydrazone (PIH) analogs, desferrithiocin (DFT) analogs, tachpyridine, the heterocyclic carboxaldehyde thiosemicarbazones, and O-Trensox [9].

Anatomical context of Desferrithiocin

• The effect of desferrithiocin, an oral iron chelator, on T-cell function [1].
• The activity of desferrioxamine (Desferal) and desferrithiocin (a newly developed oral iron chelator) was evaluated against the liver stage of Plasmodium yoelii and P. falciparum in the rodent and the human hepatocyte in vitro culture system [10].

Associations of Desferrithiocin with other chemical compounds

• Like deferoxamine, desferrithiocin inhibited, in a dose-dependent fashion, mitogen- and lectin-induced proliferation of both human and murine T cells [1].
• These inhibitory substances were: the iron chelators desferrioxamine and desferrithiocin; the electron acceptor ferricyanide; the anti-oxidant nordihydroguaiaretic acid; ebselen, an agent with glutathione peroxidase-like activity; and diphenylene iodonium, an inhibitor of NADPH-oxidase [11].

Analytical, diagnostic and therapeutic context of Desferrithiocin

• This investigation thus demonstrates which structural components of the siderophore are required for iron clearance after oral administration and suggests the use of the desferrithiocin platform as a vector for other chelators [12].
• Two protocols were investigated: "treated" recipients received desferrithiocin (30 mg/kg/day) orally for 10 days beginning the day of transplantation; "pretreated" hosts received a similar dose of the drug for 10 days before engraftment [13].
• A subgroup of the orthosubstituted phenolate class of Fe chelators, desferrithiocin [2-(3'-hydroxypyrid-2'-yl)4-methyl-delta2-thiazoline-4(S)-carboxylic acid; DFT] and its analogues, have potential application in short-term chemotherapy for cancer by Fe deprivation [14].
• The efficacy and toxicity of the siderophore desferrithiocin (DFT), which has shown potential application in iron chelation therapy, were assessed in vivo and in vitro [15].
• Oral iron chelator desferrithiocin blocks allogeneic mononuclear cell activation and cytokine production in vivo and prolongs rat cardiac allograft survival [16].

References