Targeting Iron in Colon Cancer via Glycoconjugation of Thiosemicarbazone Prochelators

Eman A. Akam, Elisa Tomat

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

The implication of iron in the pathophysiology of colorectal cancer is documented at both the biochemical and epidemiological levels. Iron chelators are therefore useful molecular tools for the study and potential treatment of this type of cancer characterized by high incidence and mortality rates. We report a novel prochelation strategy that utilizes a disulfide redox switch to connect a thiosemicarbazone iron-binding unit with carbohydrate moieties targeting the increased expression of glucose transporters in colorectal cancer cells. We synthesized three glycoconjugates (GA2TC4, G6TC4, and M6TC4) with different connectivity and/or carbohydrate moieties, as well as an aglycone analog (ATC4). The sugar conjugates present increased solubility in neutral aqueous solutions, and the ester-linked conjugates M6TC4 and G6TC4 compete as effectively as d-glucose for transporter-mediated cellular uptake. The glycoconjugates show improved selectivity compared to the aglycone analog and are 6-11 times more toxic in Caco-2 colorectal adenocarcinoma cells than in normal CCD18-co colon fibroblasts.

Original languageEnglish (US)
Pages (from-to)1807-1812
Number of pages6
JournalBioconjugate Chemistry
Volume27
Issue number8
DOIs
StatePublished - Aug 17 2016

Fingerprint

Thiosemicarbazones
Colonic Neoplasms
Glycoconjugates
Facilitative Glucose Transport Proteins
Iron
Carbohydrates
Glucose
Colorectal Neoplasms
Poisons
Fibroblasts
Chelating Agents
Sugars
Disulfides
Solubility
Oxidation-Reduction
Esters
Colon
Adenocarcinoma
Cells
Switches

ASJC Scopus subject areas

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry

Cite this

Targeting Iron in Colon Cancer via Glycoconjugation of Thiosemicarbazone Prochelators. / Akam, Eman A.; Tomat, Elisa.

In: Bioconjugate Chemistry, Vol. 27, No. 8, 17.08.2016, p. 1807-1812.

Research output: Contribution to journalArticle

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