Bio-evaluation of fluoro and trifluoromethyl-substituted salicylanilides against multidrug-resistant S. aureus.
Bio-evaluation of fluoro and trifluoromethyl-substituted salicylanilides against multidrug-resistant S. aureus.
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DOI：
10.1007/s00044-021-02808-4
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Reddy DN
中科院分区：
文献类型：
--
作者：
Lal J;Kaul G;Akhir A;Ansari SB;Chopra S;Reddy DN
耐甲氧西林金黄色葡萄球菌 (MRSA) 和耐万古霉素金黄色葡萄球菌 (VRSA) 是全世界皮肤和软组织感染的主要原因。为了解决日益增加的多重耐药（MDR）细菌感染引起的紧急情况，合成了一系列新型氟和三氟甲基取代的水杨酰苯胺衍生物，并研究了它们的抗菌活性。 MIC 数据显示，这些化合物特异性抑制金黄色葡萄球菌（MIC 0.25–64μg/mL）。 MIC<11μg/mL 的化合物对 Vero 细胞的体外细胞毒性导致鉴定出选择性指数高于 10 的四种化合物（20、22、24 和 25）。这四种化合物针对 MDR 金黄色葡萄球菌组进行了测试。值得注意的是，5-氯-N-(4'-溴-3'-三氟甲基苯基)-2-羟基苯甲酰胺 (22) 对 9 种 MRSA 和 3 种 VRSA 菌株表现出优异的活性，MIC 为 0.031–0.062 µg/mL，明显优于对照药物甲氧西林和万古霉素。比较时间-杀灭动力学实验表明，22的杀灭细菌效果与万古霉素相当。化合物 22 不会与 FDA 批准的任何抗生素产生协同作用或拮抗作用，并且比万古霉素更好地减少预先形成的金黄色葡萄球菌生物膜。总体而言，研究表明 22 可以进一步开发为有效的抗葡萄球菌疗法。
Methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Staphylococcus aureus (VRSA) are primary causes of skin and soft tissue infections worldwide. To address the emergency caused due to increasing multidrug-resistant (MDR) bacterial infections, a series of novel fluoro and trifluoromethyl-substituted salicylanilide derivatives were synthesized and their antimicrobial activity was investigated. MIC data reveal that the compounds inhibited S. aureus specifically (MIC 0.25–64 µg/mL). The in vitro cytotoxicity of compounds with MIC < 1 µg/mL against Vero cells led to identification of four compounds (20, 22, 24 and 25) with selectivity index above 10. These four compounds were tested against MDR S. aureus panel. Remarkably, 5-chloro-N-(4’-bromo-3’-trifluoromethylphenyl)-2-hydroxybenzamide (22) demonstrated excellent activity against nine MRSA and three VRSA strains with MIC 0.031–0.062 µg/mL, which is significantly better than the control drugs methicillin and vancomycin. The comparative time–kill kinetic experiment revealed that the effect of bacterial killing of 22 is comparable with vancomycin. Compound 22 did not synergize with or antagonize any FDA-approved antibiotic and reduced pre-formed S. aureus biofilm better than vancomycin. Overall, study suggested that 22 could be further developed as a potent anti-staphylococcal therapeutic.
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DOI：
10.1016/j.ijantimicag.2018.02.003
发表时间：
2018-06-01
影响因子：
10.8
作者：
Mohammad, Haroon;AbdelKhalek, Ahmed;Seleem, Mohamed N.
通讯作者：
Seleem, Mohamed N.
影响因子：
1.1
作者：
Gade ND;Qazi MS
通讯作者：
Qazi MS
影响因子：
3.5
作者：
Lee, Ill-Young;Gruber, Todd D.;Barry, Clifton E., III
通讯作者：
Barry, Clifton E., III
影响因子：
2.7
作者：
Imramovsky, Ales;Vinsova, Jarmila;Jampilek, Josef
通讯作者：
Jampilek, Josef
影响因子：
1.6
作者：
Loomba, Poonam Sood;Taneja, Juhi;Mishra, Bibhabati
通讯作者：
Mishra, Bibhabati