Monteiro Luís P G, Gomes A, Silva C, Mendes Ricardo F, Almeida Paz Filipe A, Chernyshov Dmitry, Rocha J, Martel F, Santos T M, Ferreira B J M Leite
Department of Chemistry and CICECO-Aveiro Institute of Materials, University of Aveiro, 3810-193, Aveiro, Portugal.
Biochemistry Unit, Biomedicine Department, Faculty of Medicine, University of Porto, 4200-319, Porto, Portugal.
Heliyon. 2024 Dec 18;11(1):e41323. doi: 10.1016/j.heliyon.2024.e41323. eCollection 2025 Jan 15.
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 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.
本研究报告了一种采用微波辅助合成法（MWAS）合成的铜金属配合物，该配合物由非甾体抗炎药（NSAID）布洛芬和2,2'-联吡啶胺组成。据作者所知，这是第一项报道通过微波辅助合成法制备的基于非甾体抗炎药的配合物的研究。通过元素分析、傅里叶变换红外光谱、热重分析和紫外-可见分光光度法对该配位化合物进行了表征。此外，利用同步辐射单晶X射线衍射阐明了铜金属配合物的晶体结构。通过紫外-可见光谱、圆二色光谱和荧光光谱评估了该化合物与生物分子牛血清白蛋白（BSA）和小牛胸腺DNA（CT-DNA）的相互作用。我们的研究结果表明，该金属配合物能有效地与BSA结合，导致其固有荧光和α-螺旋含量降低，并显示出在CT-DNA碱基对之间插入的能力。最后，通过MTT（3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐）法评估，该铜化合物对人乳腺癌细胞系（MCF-7和MDA-MB-231）表现出有前景的抗肿瘤活性（尽管对非肿瘤上皮癌细胞系MCF-12A也发现了类似的细胞毒性作用），并且通过硫代巴比妥酸反应物质（TBARS）法和评估谷胱甘肽水平评估发现其氧化应激水平升高。结果表明，该金属配合物通过增加氧化应激水平促进脂质过氧化，导致两种乳腺癌细胞系的活力降低。
