Towards targeted cancer therapy: Synthesis, characterization, and biological activity of a new Cu(II)-ibuprofen-2,2′-dipyridylamine metal complex

This work reports the synthesis of a copper metal complex with the nonsteroidal anti-inflammatory drug (NSAID) ibuprofen, and 2,2'-dipyridylamine employing microwave-assisted synthesis (MWAS). To the best of authors knowledge, this is the first study reporting a NSAID-based complex achieved through MWAS. The coordination compound was characterised by elemental analysis, Fourier transform infrared spectroscopy, thermogravimetry, and ultraviolet-visible spectrophotometry. Additionally, the crystal structure of the copper metal complex was elucidated using single-crystal X-ray diffraction with synchrotron radiation. The compound's interaction with the biomolecules bovine serum albumin (BSA) and calf-thymus DNA (CT-DNA), was assessed through UV-Vis, circular dichroism, and fluorescence spectroscopy. Our findings demonstrate that the metal complex effectively binds to BSA, causing a reduction in its intrinsic fluorescence and α-helical content, and shows a capacity for intercalation between CT-DNA base pairs. Finally, the copper compound exhibited promising <i>in vitro</i> antitumoral activities against human breast cancer cell lines (MCF-7 and MDA-MB-231), as evaluated by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay (although a similar cytotoxic effect against a non-tumoral epithelial cancer cell line, MCF-12A, was found), and increased oxidative stress levels as assessed by the TBARS (thiobarbituric acid reactive substances) assay and by evaluating glutathione levels. The results suggest that the metal complex promotes lipid peroxidation by increasing oxidative stress levels, leading to a reduction in viability of the two breast cancer cell lines.