From a library of compounds, 11 hit antibacterial agents have been identified as potent anti-Gram-positive bacterial agents. These pyrazole derivatives are active against two groups of pathogens, staphylococci and enterococci, with minimum inhibitory concentration (MIC) values as low as 0.78 μg/mL. These potent compounds showed bactericidal action, and some were effective at inhibiting and eradicating Staphylococcus aureus and Enterococcus faecalis biofilms. Real-time biofilm inhibition by the potent compounds was studied, by using Bioscreen C. These lead compounds were also very potent against S. aureus persisters as compared to controls, gentamycin and vancomycin. In multiple passage studies, bacteria developed little resistance to these compounds (no more than 2 × MIC). The plausible mode of action of the lead compounds is the permeabilization of the cell membrane determined by flow cytometry and protein leakage assays. With the detailed antimicrobial studies, both in planktonic and biofilm contexts, some of these potent compounds have the potential for further antimicrobial drug development.

中文翻译：

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4-[4-(苯胺基甲基)-3-苯基-吡唑-1-基]苯甲酸衍生物作为有效抗葡萄球菌和抗肠球菌药物的开发


从化合物库中，11 种热门抗菌剂已被鉴定为有效的抗革兰氏阳性细菌剂。这些吡唑衍生物对葡萄球菌和肠球菌这两组病原体具有活性，最低抑菌浓度 (MIC) 值低至 0.78 μg/mL。这些有效的化合物具有杀菌作用，其中一些可有效抑制和根除金黄色葡萄球菌和粪肠球菌生物膜。使用 Bioscreen C 研究了有效化合物的实时生物膜抑制作用。与对照、庆大霉素和万古霉素相比，这些先导化合物对金黄色葡萄球菌持续存在也非常有效。在多次传代研究中，细菌对这些化合物几乎没有产生耐药性（不超过 2 × MIC）。先导化合物的可能作用模式是通过流式细胞术和蛋白质渗漏测定确定的细胞膜的透化作用。通过在浮游生物和生物膜环境中进行详细的抗菌研究，其中一些有效的化合物具有进一步开发抗菌药物的潜力。