Preliminary evaluation of the cytotoxicity of a series of tris-2-aminoethylamine (Tren) based hexadentate heterocyclic donor agents

Bioorg Med Chem. 2005 Nov 1;13(21):5961-7. doi: 10.1016/j.bmc.2005.07.007.


Tachpyridine is a cytotoxic metal chelator with potential anti-tumor activity. The synthesis and evaluation of a set of derivatives of the related hexadentate heterocyclic donor agents tris-2-aminoethylamine (tren) and tris[N-(2-pyridylmethylene)-2-aminoethyl]amine (trenpyr) was performed to compare their cytotoxic activity to tachpyridine in HeLa tumor cells. Methyl groups were added to the pyridyl ring of trenpyr, and the effects of alkyl group substitution on cell survival were assessed. Profound cytotoxicity was observed and IC50 data were obtained in ascending order from those compounds substituted with a methyl group at the 3-, 4-, or 5-position and lastly by the 6-methyl derivative. These results suggest that analogous derivatives with substitution at the 3-position of the pyridyl ring deserve further exploration.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Cell Survival / drug effects
  • Chelating Agents / chemical synthesis
  • Chelating Agents / chemistry
  • Chelating Agents / toxicity
  • Ethylenediamines / chemical synthesis
  • Ethylenediamines / chemistry*
  • Ethylenediamines / toxicity*
  • HeLa Cells
  • Humans
  • Inhibitory Concentration 50
  • Ligands
  • Molecular Structure
  • Structure-Activity Relationship


  • Chelating Agents
  • Ethylenediamines
  • Ligands
  • tris(2-aminoethyl)amine