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

• Published in: European journal of medicinal chemistry 2014-05, Vol.78, p.383-391
• Main Authors: Papazoglou, I, Cox, P J, Hatzidimitriou, A G, Kokotidou, C, Choli-Papadopoulou, T, Aslanidis, P
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Bromides - chemistry; Cell Line; Cell Proliferation - drug effects; Chlorides - chemistry; Copper - chemistry; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; HeLa Cells; Humans; Iodides - chemistry; Models, Molecular; Molecular Structure; Organometallic Compounds - chemical synthesis; Organometallic Compounds - chemistry; Organometallic Compounds - pharmacology; Structure-Activity Relationship; Thiouracil - analogs & derivatives; Thiouracil - chemistry
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2014.03.052

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.