Synthesis of TPEN variants to improve cancer cells selective killing capacity

Research output: Contribution to journalArticle

Abstract

TPEN is an amino chelator of transition metals that is effective at the cellular and whole organism levels. Although TPEN of often used as a selective zinc chelators, it has affinity for copper and iron and has been shown to chelate both biologically. We have previously shown that TPEN selectively kills colon cancer cells based on its ability to chelate copper, which is highly enriched in colon cancer cells. The TPEN-copper complex is redox active thus allowing for increased ROS production in cancer cells and as such cellular toxicity. Here we generate TPEN derivatives with the goal of increasing its selectivity for copper while minimizing zinc chelation to reduce potential side effects. We show that one of these derivatives, TPEEN despite the fact that it exhibits reduced affinity for transition metals, is effective at inducing cell death in breast cancer cells, and exhibits less toxicity to normal breast cells. The toxicity effect of the both chelators coupled to the metal content of the different cell types reveals that they exhibit their toxicity through chelating redox active metals (iron and copper). As such TPEEN is an important novel chelators that can be exploited in anti-cancer therapies.

Original languageEnglish
Pages (from-to)366-372
Number of pages7
JournalBioorganic Chemistry
Volume87
DOIs
Publication statusPublished - 1 Jun 2019

Fingerprint

Copper
Chelating Agents
Cells
Toxicity
Metals
Neoplasms
Chelation
Transition metals
Zinc
Colonic Neoplasms
Iron
Oxidation-Reduction
Derivatives
Cell death
N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine
Breast
Cell Death
Breast Neoplasms
Therapeutics

Keywords

  • Cancer
  • Cell death
  • ROS
  • TPEN
  • Transition metals

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Drug Discovery
  • Organic Chemistry

Cite this

Synthesis of TPEN variants to improve cancer cells selective killing capacity. / Ramadan, Stephanie; Barlog, Maciej; Roach, Jim; Al-Hashimi, Mohammed; Bazzi, Hassan S.; Machaca, Khaled.

In: Bioorganic Chemistry, Vol. 87, 01.06.2019, p. 366-372.

Research output: Contribution to journalArticle

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AU - Machaca, Khaled

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