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槲皮素配合物对肺炎链球菌的治疗潜力活性。

Therapeutic potential activity of quercetin complexes against Streptococcus pneumoniae.

机构信息

Botany and Microbiology Department, Faculty of Science, Helwan University, Ain Helwan, Cairo, 11795, Egypt.

出版信息

Sci Rep. 2024 Jun 5;14(1):12876. doi: 10.1038/s41598-024-62782-w.

Abstract

This study investigates quercetin complexes as potential synergistic agents against the important respiratory pathogen Streptococcus pneumoniae. Six quercetin complexes (QCX1-6) were synthesized by reacting quercetin with various metal salts and boronic acids and characterized using FTIR spectroscopy. Their antibacterial activity alone and in synergism with antibiotics was evaluated against S. pneumoniae ATCC 49619 using disc diffusion screening, broth microdilution MIC determination, and checkerboard assays. Complexes QCX-3 and QCX-4 demonstrated synergy when combined with levofloxacin via fractional inhibitory concentration indices ≤ 0.5 as confirmed by time-kill kinetics. Molecular docking elucidated interactions of these combinations with virulence enzymes sortase A and sialidase. A biofilm inhibition assay found the synergistic combinations more potently reduced biofilm formation versus monotherapy. Additionally, gene-gene interaction networks, biological activity predictions and in-silico toxicity profiling provided insights into potential mechanisms of action and safety.

摘要

本研究探讨了槲皮素配合物作为对抗重要呼吸道病原体肺炎链球菌的潜在协同剂。通过将槲皮素与各种金属盐和硼酸反应,合成了六种槲皮素配合物(QCX1-6),并通过傅里叶变换红外光谱法对其进行了表征。使用圆盘扩散筛选、肉汤微量稀释 MIC 测定和棋盘试验,评估了它们单独以及与抗生素协同作用对 S. pneumoniae ATCC 49619 的抗菌活性。通过时间杀伤动力学证实,配合物 QCX-3 和 QCX-4 与左氧氟沙星联合使用时,通过分数抑菌浓度指数≤0.5 表现出协同作用。分子对接阐明了这些组合与毒力酶天冬酰胺酶和唾液酸酶的相互作用。生物膜抑制试验发现,与单药治疗相比,协同组合更有效地抑制生物膜形成。此外,基因-基因相互作用网络、生物活性预测和计算机毒性分析为作用机制和安全性提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/55dc/11150394/5a22da24367c/41598_2024_62782_Fig1_HTML.jpg

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