The medicinal chemistry of novel iron chelators for the treatment of cancer

Kovacevic, Zaklina, Kalinowski, Danuta S., Lovejoy, David B., Yu, Yu, Rahmanto, Yohan Suryo, Sharpe, Phillip C., Bernhardt, Paul V. and Richardson, Des R. (2011) The medicinal chemistry of novel iron chelators for the treatment of cancer. Current Topics in Medicinal Chemistry, 11 5: 483-499. doi:10.2174/156802611794785190

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Author Kovacevic, Zaklina
Kalinowski, Danuta S.
Lovejoy, David B.
Yu, Yu
Rahmanto, Yohan Suryo
Sharpe, Phillip C.
Bernhardt, Paul V.
Richardson, Des R.
Title The medicinal chemistry of novel iron chelators for the treatment of cancer
Journal name Current Topics in Medicinal Chemistry   Check publisher's open access policy
ISSN 1568-0266
1873-4294
Publication date 2011-03
Sub-type Article (original research)
DOI 10.2174/156802611794785190
Volume 11
Issue 5
Start page 483
End page 499
Total pages 17
Editor Allen B. Reitz
Place of publication Bussum, Netherlands
Publisher Bentham Science Publishers
Collection year 2012
Language eng
Formatted abstract
Cancer is one of the leading causes of death worldwide and there is an increasing need for novel anti-tumor therapeutics with greater selectivity and potency. A new strategy in the treatment of cancer has focused on targeting an essential cell metabolite, iron (Fe). Iron is vital for cell growth and metabolism, forming a crucial component of the active site of ribonucleotide reductase (RR), the rate-limiting enzyme in DNA synthesis. Cancer cells in particular require large amounts of Fe to proliferate, making them more susceptible to the Fe deficiency caused by Fe chelators. Beginning with primordial siderophores, Fe chelators have since evolved to a new generation of potent and efficient anti-cancer agents. Recently, investigations have led to the generation of novel di-2-pyridylketone thiosemicarbazone (DpT) and 2-benzoylpyridine thiosemicarbazone (BpT) ligands that demonstrate marked and selective anti-tumor activity both in vitro and in vivo against a wide spectrum of tumors. The mechanism of action of these novel ligands includes alterations in the expression of key regulatory molecules as well as the generation of redox active Fe complexes. Interestingly, nonsynthetic Fe chelators including silybin and curcumin, both of which are derived from plants, also have a high potential in the treatment of cancer. This review explores the development of novel Fe chelators for the treatment of cancer and their mechanisms of action.
Keyword Cancer
Chelators
Complexes
Iron
Thiosemicarbazones
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
School of Chemistry and Molecular Biosciences
 
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Citation counts: TR Web of Science Citation Count  Cited 43 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 16 Feb 2012, 15:50:42 EST by Lucy O'Brien on behalf of School of Chemistry & Molecular Biosciences