Suppr超能文献

含抗真菌唑类药物的银(I)配合物:唑类药物与银(I)离子配位后,抗真菌活性显著提高。

Silver(I) complexes containing antifungal azoles: significant improvement of the anti- potential of the azole drug after its coordination to the silver(I) ion.

机构信息

University of Kragujevac, Faculty of Science, Department of Chemistry, R. Domanovića 12, 34000 Kragujevac, Serbia.

University of Ljubljana, Faculty of Chemistry and Chemical Technology, Večna pot 113, SI-1000, Ljubljana, Slovenia.

出版信息

Dalton Trans. 2024 Jan 30;53(5):2218-2230. doi: 10.1039/d3dt03010e.

Abstract

Inspired by the emergence of resistance to currently available antifungal therapy and by the great potential of metal complexes for the treatment of various diseases, we synthesized three new silver(I) complexes containing clinically used antifungal azoles as ligands, [Ag(ecz)]SbF (1, ecz is econazole), {[Ag(vcz)]SbF} (2, vcz is voriconazole), and [Ag(ctz)]SbF (3, ctz is clotrimazole), and investigated their antimicrobial properties. The synthesized complexes were characterized by mass spectrometry, IR, UV-vis and H NMR spectroscopy, cyclic voltammetry, and single-crystal X-ray diffraction analysis. In the mononuclear complexes 1 and 3 with ecz and ctz, respectively, the silver(I) ion has the expected linear geometry, in which the azoles are monodentately coordinated to this metal center through the N3 imidazole nitrogen atom. In contrast, the vcz-containing complex 2 has a polymeric structure in the solid state in which the silver(I) ions are coordinated by four nitrogen atoms in a distorted tetrahedral geometry. DFT calculations were done to predict the most favorable structures of the studied complexes in DMSO solution. All the studied silver(I) complexes have shown excellent antifungal and good to moderate antibacterial activities with minimal inhibitory concentration (MIC) values in the ranges of 0.01-27.1 and 2.61-47.9 μM on the selected panel of fungi and bacteria, respectively. Importantly, the complexes 1-3 have exhibited a significantly improved antifungal activity compared to the free azoles, with the most pronounced effect observed in the case of complex 2 compared to the parent vcz against with an increase of activity by five orders of magnitude. Moreover, the silver(I)-azole complexes 2 and 3 significantly inhibited the formation of hyphae and biofilms at the subinhibitory concentration of 50% MIC. To investigate the impact of the complex 3 more thoroughly on pathogenesis, its effect on the adherence of to A549 cells (human adenocarcinoma alveolar basal epithelial cells), as an initial step of the invasion of host cells, was studied.

摘要

受目前可用抗真菌疗法出现耐药性的启发,以及金属配合物在治疗各种疾病方面的巨大潜力的启发,我们合成了三种含有临床使用的抗真菌唑类药物作为配体的新型银(I)配合物,[Ag(ecz)]SbF(1,ecz 是酮康唑)、{[Ag(vcz)]SbF}(2,vcz 是伏立康唑)和[Ag(ctz)]SbF(3,ctz 是克霉唑),并研究了它们的抗菌性能。合成的配合物通过质谱、IR、UV-vis 和 H NMR 光谱、循环伏安法和单晶 X 射线衍射分析进行了表征。在单核配合物 1 和 3 中,分别与 ecz 和 ctz 结合,银(I)离子具有预期的线性几何形状,其中唑类通过 N3 咪唑氮原子单齿配位到该金属中心。相比之下,含 vcz 的配合物 2 在固态中具有聚合结构,其中银(I)离子通过四个氮原子在扭曲的四面体几何形状中配位。进行了 DFT 计算以预测研究配合物在 DMSO 溶液中的最稳定结构。所有研究的银(I)配合物都表现出优异的抗真菌活性和良好到中等的抗细菌活性,在所选择的真菌和细菌测试组中,最小抑菌浓度(MIC)值分别在 0.01-27.1 和 2.61-47.9 μM 的范围内。重要的是,与游离唑类相比,配合物 1-3 表现出显著提高的抗真菌活性,其中配合物 2 与母体 vcz 相比,对 活性增加了五个数量级,效果最为明显。此外,银(I)-唑类配合物 2 和 3 在亚抑菌浓度 50%MIC 时显著抑制 菌丝和生物膜的形成。为了更深入地研究配合物 3 对发病机制的影响,研究了其对 黏附到 A549 细胞(人腺癌细胞肺泡基底上皮细胞)的影响,作为宿主细胞入侵的初始步骤。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验