Diethylentriaminepenta acetic acid glucose conjugates as a cell permeable iron chelator

J Pharmacol Pharmacother. 2014 Jan;5(1):27-32. doi: 10.4103/0976-500X.124416.


Objective: To find out whether DTPA-DG complex can enhance clearance of intracellular free iron.

Materials and methods: Diethylenetriaminepentaacetic acid-D-deoxy-glucosamine (DTPA-DG) was synthesized and examined for its activity as a cell-permeable iron chelator in human hepatocellular carcinoma (HEPG2) cell line exposed to high concentration of iron sulfate and compared with deferoxamine (DFO), a prototype iron chelator. The effect of DTPA-DG on cell viability was monitored using the 3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide MTT assay as well.

Results: There was a significant increase of iron level after iron overload induction in HEPG2 cell culture. DTPA-DG presented a remarkable capacity to iron burden reducing with estimated 50% inhibitory concentration value of 65.77 nM. In fact, glycosyl moiety was gained access of DTPA to intracellular iron deposits through glucose transporter systems.

Conclusion: DTPA-DG, more potent than DFO to sequester deposits of free iron with no profound toxic effect. The results suggest the potential of DTPA-DG in chelating iron and permitting its excretion from primary organ storage.

Keywords: Cell-permeable; glycosyl moiety; human hepatocellular carcinoma; iron chelation; iron overload.