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, cilt.52, sa.21, ss.7048-7058, 2023 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 52 Sayı: 21
  • Basım Tarihi: 2023
  • Doi Numarası: 10.1039/d3dt00363a
  • Dergi Adı: DALTON TRANSACTIONS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Applied Science & Technology Source, Aquatic Science & Fisheries Abstracts (ASFA), Chemical Abstracts Core, Chimica, Communication Abstracts, Compendex, EMBASE, MEDLINE
  • Sayfa Sayıları: ss.7048-7058
  • Bursa Uludağ Üniversitesi Adresli: Hayır

Özet

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)center dot 4H(2)O (2), [Cu(5-FU)(dpya)(2)](NO3)center dot 2.5H(2)O (3), [Cu(5-FU)(NO3)(bpyma)]center dot 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.