Development of 4-[4-(Anilinomethyl)-3-phenyl-pyrazol-1-yl] Benzoic Acid Derivatives as Potent Anti-Staphylococci and Anti-Enterococci Agents.
Development of 4-[4-(Anilinomethyl)-3-phenyl-pyrazol-1-yl] Benzoic Acid Derivatives as Potent Anti-Staphylococci and Anti-Enterococci Agents.
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DOI：
10.3390/antibiotics11070939
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发表时间：
2022-07-13
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影响因子：
--
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中科院分区：
文献类型：
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从化合物库中，11种HIT抗菌剂已被确定为有效的抗革兰氏阳性细菌制剂。这些吡唑类化合物对葡萄球菌和肠球菌两类致病菌均有抑制作用，最低抑菌浓度为0.78μg/mL。这些有效化合物具有杀菌作用，其中一些化合物对金黄色葡萄球菌和粪肠球菌生物被膜有抑制和根除作用。用Bioscreen C研究了有效化合物对金黄色葡萄球菌的实时生物膜抑制作用。与对照组、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也有很强的抑制作用。在多次传代研究中，细菌对这些化合物的抵抗力很小(不超过2×MIC)。这些先导化合物可能的作用方式是通过流式细胞仪和蛋白质渗漏分析确定细胞膜的通透性。随着在浮游和生物膜环境中进行的详细的抗菌研究，这些有效的化合物中的一些具有进一步抗菌药物开发的潜力。
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.
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影响因子：
4
作者：
Farha, Maya A.;Leung, Alexander;Sewell, Edward W.;D'Elia, Michael A.;Allison, Sarah E.;Ejim, Linda;Pereira, Pedro M.;Pinho, Mariana G.;Wright, Gerard D.;Brown, Eric D.
通讯作者：
Brown, Eric D.
DOI：
10.3390/molecules26165083
发表时间：
2021-08-22
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Alkhaibari IS;Kc HR;Roy S;Abu-Gazleh MK;Gilmore DF;Alam MA
通讯作者：
Alam MA
DOI：
10.1016/s0140-6736(21)02724-0
发表时间：
2022-02-12
期刊：
Lancet (London, England)
影响因子：
--
作者：
Antimicrobial Resistance Collaborators
通讯作者：
Antimicrobial Resistance Collaborators
影响因子：
6.7
作者：
Hansa RK;Khan MMK;Frangie MM;Gilmore DF;Shelton RS;Savenka AV;Basnakian AG;Shuttleworth SL;Smeltzer MS;Alam MA
通讯作者：
Alam MA
影响因子：
4.1
作者：
Saleh, Ibrahim;Raj, Hansa K. C.;Alam, Mohammad A.
通讯作者：
Alam, Mohammad A.