PDF(Pubmed)
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：
这项研究调查了槲皮素复合物作为针对重要的呼吸道病原体肺炎链球菌的潜在协同剂。通过槲皮素与各种金属盐和硼酸反应合成了六个槲皮素配合物（QCX1-6），并使用FTIR光谱进行了表征。使用圆盘扩散筛选对肺炎链球菌ATCC49619评估了其单独的抗菌活性以及与抗生素的协同作用。肉汤微量稀释MIC测定，和棋盘分析。复合物QCX-3和QCX-4通过分数抑制浓度指数≤0.5与左氧氟沙星联用时表现出协同作用，如时间杀伤动力学所证实。分子对接阐明了这些组合与毒力酶分选酶A和唾液酸酶的相互作用。生物膜抑制测定发现,与单一疗法相比,协同组合更有效地减少生物膜形成。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提供了对潜在作用机制和安全性的见解.
