Copper(I) halide complexes of 5-carbethoxy-2-thiouracil: Synthesis, structure and in vitro cytotoxicity

•New copper(I) complexes containing 5-carbethoxy-2-thiouracil and triphenylphosphine.•Remarkable in vitro cytotoxicity against two carcinoma cell lines.•The mononuclear complexes possessing triphenylphosphine are highly cytotoxic.•The phosphine-free dicopper(I) complexes are only moderately cytotoxic.

5-Carbethoxy-2-thiouracil (eitotH2) reacts with copper(I) halides CuX (X = Cl, Br, I) to give dinuclear complexes of the formula [CuX(eitotH2)2]2 while mononuclear mixed-ligand complexes of the formula [CuX(PPh3)2(eitotH2)] result when the reactions are performed in the presence of two equivalents of triphenylphosphine (PPh3). The molecular structures of representative compounds from each of the above types of complexes, namely [CuI(eitotH2)2]2, [CuCl(PPh3)2(eitotH2)] and [CuBr(PPh3)2(eitotH2)] have been established by single-crystal X-ray diffraction. The new copper(I) complexes were evaluated for in vitro antitumor properties against two tumor cell lines, A549 (human pulmonary carcinoma cell line) and HeLa (human epithelial carcinoma cell line) and one normal immortalized cell line MRC5 (human fetal lung fibroblast). The mixed-ligand complexes possessing triphenylphosphine were found to be highly cytotoxic in contrast to the phosphine-free ones which inhibited cell proliferation only in relatively high concentrations.

Graphical abstract5-Carbethoxy-2-thiouracil was used as a ligand in new dinuclear and mononuclear copper(I) halide complexes of composition [CuX(eitotH2)2]2 and [CuX(eitotH2)(PPh3)2] respectively, with remarkably high in vitro cytotoxic activity against human pulmonary carcinoma cells, human fetal lung fibroblast and human epithelial carcinoma cells.Figure optionsDownload full-size imageDownload as PowerPoint slide