Toward a Rational Design of Polyamine-Based Zinc-Chelating Agents for Cancer Therapies.

In vitro viability assays against a representative panel of human cancer cell lines revealed that polyamines and displayed remarkable activity with IC values in the micromolar range. Preliminary research indicated that both compounds promoted G1 cell cycle arrest followed by cellular senescence and apoptosis. The induction of apoptotic cell death involved loss of mitochondrial outer membrane permeability and activation of caspases 3/7. Interestingly, and failed to activate cellular DNA damage response. The high intracellular zinc-chelating capacity of both compounds, deduced from the metal-specific assay and Zn stability constant values in solution, strongly supports their cytotoxicity. These data along with quantum mechanical studies have enabled to establish a precise structure-activity relationship. Moreover, and showed appropriate drug-likeness by in silico methods. Based on these promising results, and should be considered a new class of zinc-chelating anticancer agents that deserves further development.