Background:
Several metal-based molecules that display cytotoxicity against multiple cell lines have been
pursued in an attempt to fight cancer and to overcome the typical side effects of drugs like cisplatin. In this scenario,
ruthenium complexes have been extensively studied due to their activity in both in vitro and in vivo biological systems,
including various cancer cell strains.
Objective:
We aimed to developed a method to synthesize novel [Ru(NO)(bpy) 2 L] 2+ complexes containing amino acid
ligands by using an alternative Click Chemistry approach, namely the copper azide alkyne cycloaddition reaction
(CuAAC reaction), to construct nitrosyl/nitrite complexes bearing a modified lysine residue.
Methods:
We synthesized a new ligand by Click Chemistry approach, and new compounds bearing the unprecedented
ligand. Cytotoxicity was assessed by the classical MTT colorimetric assay. MCF-7 and MDA-MB-231 cells were used as
breast cancer cells models. MCF-10 was used as a model of healthy cells.
Results:
Amino acid ligands related to N 3 -Lys(Fmoc) and the new pyLys were successfully synthesized by the
diazotransfer reaction and the CuAAC reaction, respectively. The latter reaction involves coupling between N 3 -
Lys(Fmoc) and 3ethynylpyridine. Both N 3 -Lys(Fmoc) and the new pyLys were introduced into the ruthenium bipyridine
complex I, or cis[Ru II (NO)(NO 2 )(bpy) 2 ] 2+ , to generate the common nitro-based complex III, which was further
converted to the final complex IV. Results of MTT assay proved the cytotoxic effect of cis-[Ru(NO)(bpy) 2 (pyLys)](PF 6
) 2 against the mammalian breast cancer cells MCF-7 and MDA-MB231.
Conclusion:
The viability assays revealed that complex IV, bearing a NO group and a modified lysine residue, was able
to release NO and croses tumor cell membranes. In this work, the Complex IV was the most active ruthenium bipyridine
complex against the mammalian breast cancer cells MCF-7 and MDA-MB231: it was approximately twice as active as
cisplatin, whilst complexes I–III proved to be less cytotoxic than complex IV. Additional tests using healthy MCF 10A
cells showed that complexes II–IV were three- to sixfold less toxic than cisplatin, which suggested that complex IV was
selective against cancer cells.
Correction: Identification of protein targets and the mechanism of the cytotoxic action of Ipomoea turpethum extract loaded nanoparticles against breast cancer cells
