一种新的银(I)与普罗本西德的复合物:合成、表征和抗菌及广谱β-内酰胺酶(ESBL)抑制活性研究。
A new complex of silver(I) with probenecid: Synthesis, characterization, and studies of antibacterial and extended spectrum β-lactamases (ESBL) inhibition activities.
发表日期:2023 Mar 28
作者:
Wilton R Lustri, Silmara C Lazarini, Nayara Ap Simei Aquaroni, Flávia A Resende, Nadia A Aleixo, Douglas H Pereira, Bruna Cardinali Lustri, Cristiano Gallina Moreira, Camila M Ribeiro, Fernando R Pavan, Douglas H Nakahata, Adriano M Gonçalves, Nailton M Nascimento-Júnior, Pedro P Corbi
来源:
JOURNAL OF INORGANIC BIOCHEMISTRY
摘要:
本文描述了一种新颖的银(I)复合物亚硫酰胺普罗本胺(Ag-PROB)的体外抗菌和β-内酰胺酶抑制作用。基于元素分析提出了Ag-PROB复合物的配方Ag2C26H36N2O8S2·2H2O。高分辨率质谱研究揭示了分子的二聚体形式。红外、核磁共振光谱和密度泛函理论计算表明,普罗本胺的羧酸氧原子与银离子之间采取双齿配位。Ag-PROB的体外抗菌活性表现出对结核分枝杆菌、金黄色葡萄球菌、产生生物膜的铜绿假单胞菌PA01、蜡样芽孢杆菌和大肠杆菌的显著抑制作用。Ag-PROB复合物对多重耐药性的泌尿道致病性大肠杆菌的扩展谱β-内酰胺酶产生的(EC958和BR43)、肠出血性大肠杆菌(O157:H7)和肠毒性聚集杆菌(O104:H4)也有活性。Ag-PROB能够在存在氨苄青霉素(AMP)浓度的情况下抑制CTX-M-15和TEM-1B ESBL类,而EC958和BR43细菌在没有Ag-PROB的情况下对其具有抗药性。这些结果表明,除了ESBL的抑制,AMP和Ag-PROB之间存在协同的抗菌效应。分子对接结果揭示了Ag-PROB、CTX-M-15和TEM1B之间相互作用的可能的关键残基,从而揭示ESBL抑制的分子机制。所得结果加上Ag-PROB复合物对非肿瘤细胞的无致突变活性和低细胞毒活性,为其未来作为抗菌剂使用的体内试验打开了新的前景。版权所有©2023 Elsevier Inc.发布。
This article describes the in vitro antibacterial and β-lactamase inhibition of a novel silver(I) complex with the sulfonamide probenecid (Ag-PROB). The formula Ag2C26H36N2O8S2·2H2O for the Ag-PROB complex was proposed based on elemental analysis. High-resolution mass spectrometric studies revealed the existence of the complex in its dimeric form. Infrared, nuclear magnetic resonance spectroscopies and Density Functional Theory calculations indicated a bidentate coordination of probenecid to the silver ions by the oxygen atoms of the carboxylate. In vitro antibacterial activities of Ag-PROB showed significant growth inhibitory activity over Mycobacterium tuberculosis, S. aureus, and P. aeruginosa PA01biofilm-producers, B. cereus, and E. coli. The Ag-PROB complex was active over multi-drug resistant of uropathogenic E. coli extended spectrum β-lactamases (ESBL) producing (EC958 and BR43), enterohemorrhagic E. coli (O157:H7) and enteroaggregative E. coli (O104:H4). Ag-PROB was able to inhibit CTX-M-15 and TEM-1B ESBL classes, at concentrations below the minimum inhibitory concentration for Ag-PROB, in the presence of ampicillin (AMP) concentration in which EC958 and BR43 bacteria were resistant in the absence of Ag-PROB. These results indicate that, in addition to ESBL inhibition, there is a synergistic antibacterial effect between AMP and the Ag-PROB. Molecular docking results revealed potential key residues involved in interactions between Ag-PROB, CTX-M-15 and TEM1B, suggesting the molecular mechanism of the ESBL inhibition. The obtained results added to the absence of mutagenic activity and low cytotoxic activity over non-tumor cell of the Ag-PROB complex open a new perspective for future in vivo tests demonstrating its potential of use as an antibacterial agent.Copyright © 2023. Published by Elsevier Inc.