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含哒嗪羧酸的钌配合物:合成、表征及抗生物膜活性

Ruthenium Complexes with Pyridazine Carboxylic Acid: Synthesis, Characterization, and Anti-Biofilm Activity.

作者信息

Rogala Patrycja, Jabłońska-Wawrzycka Agnieszka, Czerwonka Grzegorz, Hodorowicz Maciej, Michałkiewicz Sławomir, Kalinowska-Tłuścik Justyna, Karpiel Marta, Gałczyńska Katarzyna

机构信息

Institute of Chemistry, Jan Kochanowski University, 7 Uniwersytecka Str., 25-406 Kielce, Poland.

Institute of Biology, Jan Kochanowski University, 7 Uniwersytecka Str., 25-406 Kielce, Poland.

出版信息

Molecules. 2024 Dec 2;29(23):5694. doi: 10.3390/molecules29235694.

Abstract

As a result of drug resistance, many antimicrobial medicines become ineffective, making the infections more difficult to treat. Therefore, there is a need to develop new compounds with antibacterial activity. This role may be played, for example, by metal complexes with carboxylic acids. This study reports the formation and characterization of ruthenium complexes with pyridazine-3-carboxylic acid (pdz-3-COOH)-([(η--cym)RuCl(pdz-3-COO)] (), RuCl(pdz-3-COO)Na(HO) () and [RuCl(pdz-3-COO)Na(HO)] (). The synthesized compounds were analyzed using various spectroscopic and electrochemical techniques, with structure confirmation via SC-XRD analysis. Experimental data showed the ligand binds to metal ions bidentately through the nitrogen donor of the pyridazine ring and one carboxylate oxygen. To visualize intermolecular interactions, Hirshfeld surface analysis and 2D fingerprint plots were conducted. Furthermore, the impact of ruthenium compounds ( and ) on the planktonic growth of selected bacterial strains and the formation of PAO1 biofilm was examined. Both complexes demonstrated comparable anti-biofilm activity and outperformed the free ligand. The effect of the complexes on selected virulence factors of PAO1 was also investigated. Compounds and show high suppressive activity in pyoverdine production, indicating that the virulence of the strain has been reduced. This inhibitory effect is similar to the inhibitory effect of ciprofloxacin. Within this context, the complexes exhibit promising antibacterial activities. Importantly, the compounds showed no cytotoxic effects on normal CHO-K1 cells. Additionally, a molecular docking approach and fluorescence spectroscopy were used to determine the interactions of ruthenium complexes with human serum albumin.

摘要

由于耐药性,许多抗菌药物变得无效,使感染更难治疗。因此,需要开发具有抗菌活性的新化合物。例如,羧酸金属配合物可能发挥这一作用。本研究报告了钌与哒嗪 - 3 - 羧酸(pdz - 3 - COOH)形成的配合物的合成与表征 - ([(η - 对异丙基苯)RuCl(pdz - 3 - COO)](),[RuCl(pdz - 3 - COO)Na(H₂O)](H₂O)()和[RuCl(pdz - 3 - COO)Na(H₂O)]()。使用各种光谱和电化学技术对合成的化合物进行了分析,并通过单晶X射线衍射分析确认了结构。实验数据表明,配体通过哒嗪环的氮供体和一个羧酸根氧与金属离子双齿配位。为了可视化分子间相互作用,进行了 Hirshfeld 表面分析和二维指纹图谱分析。此外,还研究了钌化合物(和)对所选细菌菌株浮游生长和PAO1生物膜形成的影响。两种配合物均表现出相当的抗生物膜活性,且优于游离配体。还研究了配合物对PAO1所选毒力因子的影响。化合物和在绿脓菌素产生方面表现出高抑制活性,表明该菌株的毒力已降低。这种抑制作用与环丙沙星的抑制作用相似。在此背景下,这些配合物表现出有前景的抗菌活性。重要的是,这些化合物对正常CHO - K1细胞没有细胞毒性作用。此外,使用分子对接方法和荧光光谱法确定了钌配合物与人血清白蛋白的相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1449/11643884/5aa3479ac171/molecules-29-05694-g001.jpg

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