Zavaroni Alessio, Rigamonti Luca, Bisceglie Franco, Carcelli Mauro, Pelosi Giorgio, Gentilomi Giovanna Angela, Rogolino Dominga, Bonvicini Francesca
Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parco Area delle Scienze 17/A, 43124 Parma, Italy.
Dipartimento di Scienze Chimiche e Geologiche, Università degli Studi di Modena e Reggio Emilia, Via G. Campi 103, 41125 Modena, Italy.
Molecules. 2025 May 26;30(11):2329. doi: 10.3390/molecules30112329.
Antibiotic resistance is a problem repeatedly reported by health authorities. Metalloantibiotics, i.e., biologically active compounds containing one or more metal ions, can be an important resource in the fight against bacteria and fungi. Here, we report the results obtained with a panel of copper(II), nickel(II) and zinc(II) complexes with thiosemicarbazone, semicarbazone and acylhydrazone ligands on , and , taken as model systems of human pathogens. To increase the solubility in water, the sulfonic group was introduced on some of the ligands, isolating them as sodium salts (NaHL4-NaHL7). Complexes - were isolated, fully characterized and the X-ray structures of , and were obtained. While all the ligands have no antimicrobial activity, the copper(II) complexes and and the nickel(II) complex , obtained from thiosemicarbazone ligands, showed good activity, in particular against ; these complexes were investigated in depth, calculating their respective IC values (4.2 μM, 3.5 μM and 61.8 μM, respectively). It should be noted that nickel(II) complex does not show hemolytic activity and has a favorable SI value. While all the copper(II) complexes completely degraded the plasmid DNA in presence of HO, nickel(II) complex cleaved the plasmid DNA leading to the formation of the relaxed nicked conformation, thus suggesting a different mechanism of action.
抗生素耐药性是卫生当局反复报告的一个问题。金属抗生素，即含有一个或多个金属离子的生物活性化合物，可能是对抗细菌和真菌的重要资源。在此，我们报告了一组铜（II）、镍（II）和锌（II）与硫代半卡巴腙、半卡巴腙和酰腙配体形成的配合物对作为人类病原体模型系统的大肠杆菌、金黄色葡萄球菌和白色念珠菌的实验结果。为了提高在水中的溶解度，在一些配体上引入了磺酸基团，并将它们分离为钠盐（NaHL4 - NaHL7）。分离并完全表征了配合物 - ，并获得了 、 和 的X射线结构。虽然所有配体均无抗菌活性，但由硫代半卡巴腙配体得到的铜（II）配合物 和 以及镍（II）配合物 表现出良好的活性，尤其是对 ；对这些配合物进行了深入研究，计算了它们各自的IC值（分别为4.2 μM、3.5 μM和61.8 μM）。应当指出的是，镍（II）配合物 不显示溶血活性且具有良好的SI值。虽然所有铜（II）配合物在过氧化氢存在下能完全降解质粒DNA，但镍（II）配合物 能切割质粒DNA导致形成松弛的切口构象，因此表明其作用机制不同。
