Water-soluble copper(II) 5-fluorouracil complexes bearing polypyridyl co-ligands: synthesis, structures and anticancer activity

İÇSEL YILMAZ C., YILMAZ V. T., AYGÜN M., Erkisa M., Ulukaya E.

Dalton transactions (Cambridge, England : 2003), vol.52, no.21, pp.7048-7058, 2023 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 52 Issue: 21
  • Publication Date: 2023
  • Doi Number: 10.1039/d3dt00363a
  • Journal Name: Dalton transactions (Cambridge, England : 2003)
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Applied Science & Technology Source
  • Page Numbers: pp.7048-7058
  • Karadeniz Technical University Affiliated: Yes


Five newly synthesized copper(II) 5-fluorouracil (5-FU) complexes of polypyridyl co-ligands with good solubility in water, namely [CuCl(5-FU)(bpy)(DMSO)] (1), [Cu(5-FU)(phen)2](5-FU)·4H2O (2), [Cu(5-FU)(dpya)2](NO3)·2.5H2O (3), [Cu(5-FU)(NO3)(bpyma)]·H2O (4) and [CuCl(5-FU)(terpy)] (5) (bpy = 2,2'-bipyridine, phen = 1,10-phenanthroline, dpya = 2,2'-dipyridylamine, bpyma = bis(2-pyridylmethyl)amine and terpy = 2,2';6',2''-terpyridine), were characterized by elemental analysis and a number of spectrometric methods. The structures of complexes 1-5 were determined by X-ray crystallography and the copper(II) ions were five coordinate. Cytotoxic activity of the complexes in four human cancer cell lines, A549 (lung carcinoma), MDA-MB-231 (breast carcinoma), HCT116 (colon carcinoma) and DU145 (prostate carcinoma), and a normal cell line, BEAS-2B (human lung epithelial), was determined by SRB assay and compared with that of 5-FU and cisplatin. The complexation of 5-FU together with polypyridyl ligands resulted in a significant increase in the cytotoxicity of the complexes, with complex 2 exhibiting the highest anticancer potency against all the cell lines, with HCT116 being the most sensitive. The mode of action of cell death for 2 was investigated using morphological imaging and cytometric analyses, including the capacity for induction of apoptosis, generation of reactive oxygen species, mitochondrial dysfunction and DNA damage.