The DOI matches its Crossref record; 85 of the 85 references it cites were found in a registry or an index.
Novel di-2-pyridyl–derived iron chelators with marked and selective antitumor activity: in vitro and in vivo assessment
Open accessAbstract
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 selective antitumor activity—for example, an IC50 of 0.03 μM in neuroepithelioma cells compared with more than 25 μM in mortal fibroblasts. Indeed, this antiproliferative activity was the greatest yet observed for an Fe chelator. Efficacy was greater than it was for the cytotoxic ligand 311 and comparable to that of the antitumor agent doxorubicin. Strikingly, Dp44mT significantly (P < .01) decreased tumor weight in mice to 47% of the weight in the control after only 5 days, whereas there was no marked change in animal weight or hematologic indices. Terminal deoxyribonucleotidyl transferase (TdT)–mediated dUTP nick end-labeling (TUNEL) staining demonstrated apoptosis in tumors taken from mice treated with Dp44mT. This chelator caused a marked increase of caspase-3 activity in murine Madison-109 (M109) cells. Caspase activation was at least partially mediated by the release of mitochondrial holo-cytochrome c (h-cytc) after incubation with Dp44mT. In conclusion, Dp44mT is a novel, highly effective antitumor agent in vitro and in vivo that induces apoptosis.
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Metadata
- Authors
- Yuan, J., Lovejoy, D. B., & Richardson, D. R.
- Venue
- Blood
- Publisher
- American Society of Hematology
- Published
- 2004-09-01
- Volume
- 104
- Issue
- 5
- Pages
- 1450-1458
- ISSN
- 0006-4971 (ISSN-L)
- 1528-0020
- OpenAlex
- W2071410533
- Cited by
- 381
- References
- 85
- FWCI
- 4.11
- Type
- journal article
- Language
- en
- Open access
- bronze
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