Department of Biochemistry and Genetics, Institute of Biology, Jan Kochanowski University, Świętokrzyska 15, 25-406, Kielce, Poland.
Holy Cross Oncology Center of Kielce, Artwińskiego 3, 25-734, Kielce, Poland.
Sci Rep. 2019 Jul 5;9(1):9777. doi: 10.1038/s41598-019-46224-6.
The physicochemical properties of metal complexes determine their potential applications as antitumor agents. In this study, the antitumor properties of mononuclear cobalt(II) and copper(II) coordination compounds (stoichiometry: [Co(iaa)(HO)]·HO (iaa = imidazole-4-acetate anion), Co(1-allim) (1-allim = 1-allylimidazole), [Cu(iaa)HO] and [Cu(1-allim)(NO)]) and their ligands have been evaluated on human lung carcinoma A549 cells and normal bronchial BEAS-2B cells. Designing the chemical structure of new antitumor agents the possible interactions with macromolecules such as DNA or proteins should be take into account. PCR gene tlr4 product served as DNA model, whereas lysozyme and phage-derived endolysin (both peptidoglycan degrading enzymes) were applied as protein/enzyme model. The interactions were analysed using PCR-HRM and circular dichroism, FT-IR, spectrophotometry, respectively. Additionally, the antimicrobial properties of the complexes at a non-cytotoxic concentration were analyzed against S. aureus, E. coli, P. aeruginosa and C. albicans strains. The results obtained in this study showed the selective cytotoxicity of metal complexes, mainly [Cu(1-allim)(NO)] towards tumor cells. From all tested compounds, only [Co(iaa)(HO)]HO non-covalently interacts with DNA. Cu(II) and Co(II) complexes did not affect the secondary conformation of tested proteins but modified the hydrolytic activity of enzymes (lysozyme and endolysin). Moreover, only [Co(iaa)(HO)]HO exhibited the antifungal properties. In conclusion, Co(II) and Cu(II) metal complexes bearing two imidazole-4-acetate ligands seemed to be promising antitumor and antifungal agents for future drug design and application.
金属配合物的物理化学性质决定了它们作为抗肿瘤剂的潜在应用。在这项研究中,单核钴(II)和铜(II)配合物(化学计量比:[Co(iaa)(HO)]·HO(iaa=咪唑-4-乙酸根阴离子),[Co(1-allim)](NO)(1-allim=1-烯丙基咪唑),[Cu(iaa)HO]和[Cu(1-allim)(NO)]及其配体在人肺癌 A549 细胞和正常支气管 BEAS-2B 细胞上的抗肿瘤特性进行了评估。设计新的抗肿瘤剂的化学结构时,应考虑与大分子如 DNA 或蛋白质的可能相互作用。PCR 基因 tlr4 产物用作 DNA 模型,而溶菌酶和噬菌体衍生的内溶素(两种肽聚糖降解酶)用作蛋白质/酶模型。使用 PCR-HRM、圆二色性、FT-IR 和分光光度法分别分析了相互作用。此外,还分析了在非细胞毒性浓度下这些配合物对金黄色葡萄球菌、大肠杆菌、铜绿假单胞菌和白色念珠菌的抗菌特性。本研究结果表明,金属配合物对肿瘤细胞具有选择性细胞毒性,主要是[Cu(1-allim)(NO)]。在所有测试的化合物中,只有[Co(iaa)(HO)]HO 与 DNA 非共价相互作用。Cu(II)和 Co(II)配合物不影响测试蛋白的二级构象,但改变了酶(溶菌酶和内溶素)的水解活性。此外,只有[Co(iaa)(HO)]HO 表现出抗真菌特性。总之,具有两个咪唑-4-乙酸配体的 Co(II)和 Cu(II)金属配合物似乎是有前途的抗肿瘤和抗真菌药物,可用于未来的药物设计和应用。