de Araújo Rodrigo Santos Aquino, Barbosa-Filho José Maria, Scotti Marcus Tullius, Scotti Luciana, da Cruz Ryldene Marques Duarte, Falcão-Silva Vivyanne Dos Santos, de Siqueira-Júnior José Pinto, Mendonça-Junior Francisco Jaime Bezerra
Post-Graduate Program in Natural and Synthetic Bioactive Products, Federal University of Paraíba, 58051-900 João Pessoa, PB, Brazil.
Laboratory of Genetics of Microorganisms, Molecular Biology Department, Federal University of Paraíba, 58051-900 João Pessoa, PB, Brazil.
Scientifica (Cairo). 2016;2016:6894758. doi: 10.1155/2016/6894758. Epub 2016 Apr 19.
Semisynthetic and commercial coumarins were investigated for their antibacterial and adjuvant properties with antibiotic agents against norfloxacin, erythromycin, and tetracycline resistant Staphylococcus aureus as based on efflux mechanisms. The coumarins and certain commercial antibiotics had their Minimum Inhibitory Concentrations determined by broth microdilution assay against resistant S. aureus strains which overexpress efflux pump proteins. For evaluation of the modulatory activity, the antibiotics MICs were determined in the presence of the coumarin derivatives at subinhibitory concentration. Although the coumarins did not display relevant antibacterial activity (MIC ≥ 128 µg/mL), they did modulate the antibiotics activities. Various coumarins, especially the alkylated derivatives in combination with antibiotics at subinhibitory concentrations, modulated antibiotic activity, reducing the MIC for tetracycline and norfloxacin by 2 to 8 times. Polar Surface Area (PSA) studies were performed and the fact that the presence of apolar groups is an important factor for the modulatory activity of coumarins was corroborated. Docking on the Penicillin-Binding Protein from MRSA identified that 18 is a potential ligand presenting low E binding. The results indicate that coumarin derivatives modulated antibiotic resistance and may be used as potential antibiotic adjuvants, acting by bacterial efflux pump inhibition in S. aureus.
基于外排机制，研究了半合成香豆素和市售香豆素与抗生素联合使用时，对耐诺氟沙星、红霉素和四环素的金黄色葡萄球菌的抗菌和佐剂特性。通过肉汤微量稀释法测定了香豆素和某些市售抗生素对过表达外排泵蛋白的耐药金黄色葡萄球菌菌株的最低抑菌浓度。为了评估调节活性，在亚抑菌浓度的香豆素衍生物存在下测定抗生素的最低抑菌浓度。尽管香豆素没有显示出相关的抗菌活性（最低抑菌浓度≥128μg/mL），但它们确实调节了抗生素的活性。各种香豆素，尤其是亚抑菌浓度下与抗生素联合使用的烷基化衍生物，调节了抗生素活性，使四环素和诺氟沙星的最低抑菌浓度降低了2至8倍。进行了极性表面积（PSA）研究，证实了非极性基团的存在是香豆素调节活性的重要因素这一事实。对耐甲氧西林金黄色葡萄球菌青霉素结合蛋白的对接分析确定18是一种具有低结合能的潜在配体。结果表明，香豆素衍生物可调节抗生素耐药性，可能作为潜在的抗生素佐剂，通过抑制金黄色葡萄球菌的细菌外排泵发挥作用。
