Design, synthesis, and antibacterial activity of N-(trifluoromethyl)phenyl substituted pyrazole derivatives
Design, synthesis, and antibacterial activity of N-(trifluoromethyl)phenyl substituted pyrazole derivatives
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DOI：
10.1039/d1md00230a
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发表时间：
2021-08-19
影响因子：
4.1
通讯作者：
Alam, Mohammad A.
中科院分区：
文献类型：
--
作者：
Saleh, Ibrahim;Raj, Hansa K. C.;Alam, Mohammad A.
设计、合成了N-（三氟甲基）苯基取代的吡唑衍生物，并对其抗菌活性进行了研究。这些新化合物中的几种是耐甲氧西林革兰氏阳性菌的有效生长抑制剂，并防止耐甲氧西林金黄色葡萄球菌（MRSA）和粪肠球菌形成生物膜。这些化合物有效地根除了预先形成的生物膜，并且被发现比对照抗生素万古霉素更有效。有效化合物对培养的人胚肾细胞显示出低毒性，选择性因子>20。最有前途的化合物是非常有效的对美罗培南，苯唑西林，万古霉素耐药临床分离的屎肠球菌。通过进行大分子合成抑制研究对作用模式进行的研究显示了广泛的抑制作用，表明靶标对细菌细胞功能具有全局影响。
Design and synthesis of N-(trifluoromethyl)phenyl substituted pyrazole derivatives and their potency as antimicrobial agents are described. Several of these novel compounds are effective growth inhibitors of antibiotic-resistant Gram-positive bacteria and prevent the development of biofilms by methicillin-resistant Staphylococcus aureus (MRSA) and Enterococcus faecalis. These compounds eradicated the preformed biofilms effectively and were found to be more effective than the control antibiotic vancomycin. Potent compounds showed low toxicity to cultured human embryonic kidney cells with a selectivity factor of >20. The most promising compound is very potent against meropenem, oxacillin, and vancomycin-resistant clinical isolates of Enterococcus faecium. Investigations into the mode of action by performing macromolecular synthesis inhibition studies showed a broad range of inhibitory effects, suggesting targets that have a global effect on bacterial cell function.