4-4-(Anilinomethyl)-3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-ylbenzoic acid derivatives as potent anti-gram-positive bacterial agents.
4-4-(Anilinomethyl)-3-[4-(trifluoromethyl)phenyl]-1H-pyrazol-1-ylbenzoic acid derivatives as potent anti-gram-positive bacterial agents.
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DOI：
10.1016/j.ejmech.2021.113402
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发表时间：
2021-07-05
影响因子：
6.7
通讯作者：
Alam MA
中科院分区：
文献类型：
--
作者：
Hansa RK;Khan MMK;Frangie MM;Gilmore DF;Shelton RS;Savenka AV;Basnakian AG;Shuttleworth SL;Smeltzer MS;Alam MA
由新型 1,3-双苯甲酸和三氟甲基苯基衍生的吡唑组成的一系列强效抗菌剂已被合成并测试了抗菌活性。大多数三氟甲基苯基衍生物是革兰氏阳性菌的高效生长抑制剂，并且对人类培养细胞的毒性较低。特别是，选择了两种化合物（59 和 74）进行进一步研究。这些化合物对金黄色葡萄球菌高度有效，表现为较低的最低抑制浓度 (MIC)、时间杀灭测定中的杀菌作用、对生物膜形成和生物膜破坏的适度抑制以及对代表非生长持续细胞的静止期细胞的杀菌作用。多步耐药性测定显示金黄色葡萄球菌和粪肠球菌通过突变产生耐药性的趋势非常低。此外，体内小鼠模型研究表明，使用 14 种血浆器官毒性标记物或肝脏和肾脏中的 TUNEL 测定，剂量高达 50 mg/kg 时没有有害影响。通过进行大分子合成抑制研究来研究作用模式，显示出广泛的抑制作用，表明对细菌细胞功能具有全局影响的靶标。
A collection of potent antimicrobials consisting of novel 1,3-bis-benzoic acid and trifluoromethyl phenyl derived pyrazoles has been synthesized and tested for antibacterial activity. The majority of trifluoromethyl phenyl derivatives are highly potent growth inhibitors of Gram-positive bacteria and showed low toxicity to human cultured cells. In particular, two compounds (59 and 74) were selected for additional studies. These compounds are highly effective against Staphylococcus aureus as shown by a low minimum inhibitory concentration (MIC), a bactericidal effect in time-kill assays, moderate inhibition of biofilm formation as well as biofilm destruction, and a bactericidal effect against stationary phase cells representing non-growing persister cells. Multistep resistance assays showed a very low tendency for S. aureus and Enterococcus faecalis to develop resistance through mutation. Additionally, in vivo mouse model studies showed no harmful effects at doses up to 50 mg/kg using 14 blood plasma organ toxicity markers or TUNEL assay in liver and kidney. 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.
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4- [4-甲酰基-3-（2-萘基）吡唑-1-基]苯甲酸衍生物的设计和合成是耐药金黄色葡萄球菌的有效生长抑制剂。
DOI：
10.1038/s41429-020-0341-2
发表时间：
2020-12
期刊：
The Journal of antibiotics
影响因子：
--
作者：
Alnufaie R;Alsup N;Kc HR;Newman M;Whitt J;Chambers SA;Gilmore D;Alam MA
通讯作者：
Alam MA
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.
影响因子：
15
作者：
Joseph, Roymon;Naugolny, Alissa;Cohen, Yoram
通讯作者：
Cohen, Yoram
影响因子：
64.5
作者：
Martin JK 2nd;Sheehan JP;Bratton BP;Moore GM;Mateus A;Li SH;Kim H;Rabinowitz JD;Typas A;Savitski MM;Wilson MZ;Gitai Z
通讯作者：
Gitai Z
影响因子：
5.2
作者：
Roy R;Tiwari M;Donelli G;Tiwari V
通讯作者：
Tiwari V