ROS dependent antitumour activity of photo-activated iron(III) complexes of amino acids

Several amino acid-based photo-active monomeric iron(III) complexes of the general formula, $[{\text{Fe(L)}}_2{]}^{-}$, where $\text{L}=$ Schiff base ligands (salisalidene arginine, salicylidenetryptophan, 3,5-di-tert-butyl benzalidine arginine and salicylidene tryptophan) were synthesized, characterized and explored for photo-activated anticancer activity to Chang Liver Cells, HeLa and MCF-7 cells. Complexes exhibited remarkable photo-cytotoxicity with ${\text{IC}}_{50}$ value to the extent of $0.7\mu \text{M}$ to Chang Liver Cells in visible light and there was a 40-fold enhancement in cytotoxicity in comparison to the cytotoxicity in dark. Complexes were non-toxic to MCF-10A (normal cells) in dark and visible light (${\text{IC}}_{50}>100\mu \text{M}$ in dark; ${\text{IC}}_{50}>80\mu \text{M}$ in visible light) signifying target-specific nature of the anti-tumour activity of the complexes. Increased ROS concentration, as probed by DCFDA assay, in the cancer cells was responsible for apoptotic cell death. Decarboxylation or phenolate-Fe(III) charge transfer of photo-activated iron(III) complexes generating ${}^{\bullet }$OH radicals (ROS) were responsible for the apoptosis. Overall, the tumour-selective photo-activated anticancer activity of the amino acid-based iron(III) complexes have shown a promising aspect in developing iron-based photo-chemotherapeutics as the next generation PDT agents.

Graphical abstract

Monomeric iron(III) complexes are explored for photo-activated antitumour activity. Photodecarboxylation or photo-induced charge transfer of phenolate-$\text{O}\to \text{Fe(III)}$ has led to the generation of hydroxyl radicals causing apoptotic cell death. .