Partition coefficients of the iron(III) complexes of pyridoxal isonicotinoyl hydrazone and its analogs and the correlation to iron chelation efficacy

Edward, John T.; Ponka, Prem; Richardson, Des R.

doi:10.1007/bf00143378

Cited by 32 publications

(19 citation statements)

References 38 publications

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“…This observation together with their marked redox activity may, in part, explain the greater cytotoxicity of the Cu complexes compared with the ligands (Jansson et al, 2010). The greater uptake of the complexes may be attributed to: 1) their increased lipophilicity versus the ligand (Edward et al, 1995); 2) differing modes of uptake; and/or 3) complex sequestration within cellular compartments, e.g., lysosomes . Interestingly, repeated administration of Dp44mT and a close analog, Bp44mT, to mice bearing tumor xenografts does not lead to tumor Fe depletion, also suggesting that Fe complexes may become sequestered in vivo Yu et al, 2012).…”

Section: Discussionmentioning

confidence: 98%

Cellular Uptake of the Antitumor Agent Dp44mT Occurs via a Carrier/Receptor-Mediated Mechanism

Merlot¹,

Pantarat²,

Menezes³

et al. 2013

Mol Pharmacol

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Section: Discussionmentioning

confidence: 98%

Cellular Uptake of the Antitumor Agent Dp44mT Occurs via a Carrier/Receptor-Mediated Mechanism

Merlot¹,

Pantarat²,

Menezes³

et al. 2013

Mol Pharmacol

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“…The lipophilicity of iron chelators affects their membrane permeability and ultimately their ability to mobilize intracellular iron [24–26] . For a comparative assessment of the lipophilicity of the new compounds, the octanol/water partition coefficients (log P o/w values) were determined using the stir‐flask method and analytical HPLC (see ESI for details).…”

Section: Figurementioning

confidence: 99%

Albumin Conjugates of Thiosemicarbazone and Imidazole‐2‐thione Prochelators: Iron Coordination and Antiproliferative Activity

Sung

Ewbank

et al. 2021

ChemMedChem

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The central role of iron in tumor progression and metastasis motivates the development of iron‐binding approaches in cancer chemotherapy. Disulfide‐based prochelators are reductively activated upon cellular uptake to liberate thiol chelators responsible for iron sequestration. Herein, a trimethyl thiosemicarbazone moiety and the imidazole‐2‐thione heterocycle are incorporated in this prochelator design. Iron binding of the corresponding tridentate chelators leads to the stabilization of a low‐spin ferric center in 2 : 1 ligand‐to‐metal complexes. Native mass spectrometry experiments show that the prochelators form stable disulfide conjugates with bovine serum albumin, thus affording novel bioconjugate prochelator systems. Antiproliferative activities at sub‐micromolar levels are recorded in a panel of breast, ovarian and colorectal cancer cells, along with significantly lower activity in normal fibroblasts.

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“…The majority of PIH analogs are relatively lipophilic, as compared to other chelators, resulting in the rapid membrane permeability of PIH [137], one of the least lipophilic compounds of the series [138]. This property likely contributes to the oral availability of the PIH analogs [139].…”

Section: Pyridoxal Isonicotinoyl Hydrazone and Analogsmentioning

confidence: 99%

The Role of Iron Chelation in Cancer Therapy

Buss¹,

Torti²,

Torti³

2003

CMC

214

216

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This review focuses on advances and strategies in the use of iron chelators as anti-tumor therapies. Although the development of iron chelators for human disease has focused primarily on their use in the treatment of secondary iron overload, chelators may also be useful anti-tumor agents. They can deplete iron or cause oxidative stress in the tumor due to redox perturbations in its environment. Iron chelators have been tested for their anti-tumor activity in cell culture experiments, animal models and human clinical trials. Largely for pragmatic reasons, clinical studies of the anti-tumor activity of iron chelators have generally focused on desferrioxamine (DFO), a drug approved for the treatment of iron overload. These studies have shown that DFO can retard tumor growth in many different experimental contexts. However, the activity of DFO is modest, and advances in the use of chelators as anti-cancer agents will require the development of new chelators based on new paradigms. Examples of iron chelators that have shown promising anti-tumor activity (in various stages of development) include heterocyclic carboxaldehyde thiosemicarbazones, analogs of pyridoxal isonicotinoyl hydrazone, tachpyridine, O-trensox, desferrithiocin, and other natural and synthetic chelators. Apart from their use as single agents, chelators may also synergize with other anti-cancer therapies. The development of chelators as anticancer agents is largely an unexplored field, but one with extraordinary potential to impact human cancer.

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Partition coefficients of the iron(III) complexes of pyridoxal isonicotinoyl hydrazone and its analogs and the correlation to iron chelation efficacy

Cited by 32 publications

References 38 publications

Cellular Uptake of the Antitumor Agent Dp44mT Occurs via a Carrier/Receptor-Mediated Mechanism

Cellular Uptake of the Antitumor Agent Dp44mT Occurs via a Carrier/Receptor-Mediated Mechanism

Albumin Conjugates of Thiosemicarbazone and Imidazole‐2‐thione Prochelators: Iron Coordination and Antiproliferative Activity

The Role of Iron Chelation in Cancer Therapy

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