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An Update on Staphylococcus aureus NorA Efflux Pump Inhibitors.
Current Topics in Medicinal Chemistry ( IF 3.4 ) Pub Date : 2020-08-31 , DOI: 10.2174/1568026620666200704135837
Kadja Luana Chagas Monteiro 1 , Thiago Mendonça de Aquino 1 , Francisco Jaime B Mendonça Junior 2
Affiliation  

Background: Methicillin-resistant and vancomycin-resistant Staphylococcus aureus are pathogens causing severe infectious diseases that pose real public health threats problems worldwide. In S. aureus, the most efficient multidrug-resistant system is the NorA efflux pump. For this reason, it is critical to identify efflux pump inhibitors.

Objective: In this paper, we present an update of the new natural and synthetic compounds that act as modulators of antibiotic resistance through the inhibition of the S. aureus NorA efflux pump.

Results: Several classes of compounds capable of restoring the antibiotic activity have been identified against resistant-S. aureus strains, acting as NorA efflux pump inhibitors. The most promising classes of compounds were quinolines, indoles, pyridines, phenols, and sulfur-containing heterocycles. However, the substantial degree structural diversity of these compounds makes it difficult to establish good structure- activity correlations that allow the design of compounds with more promising activities and properties.

Conclusion: Despite substantial efforts put forth in the search for new antibiotic adjuvants that act as efflux pump inhibitors, and despite several promising results, there are currently no efflux pump inhibitors authorized for human or veterinary use, or in clinical trials. Unfortunately, it appears that infection control strategies have remained the same since the discovery of penicillin, and that most efforts remain focused on discovering new classes of antibiotics, rather than trying to prolong the life of available antibiotics, and simultaneously fighting mechanisms of bacterial resistance.



中文翻译:

金黄色葡萄球菌NorA外排泵抑制剂的更新。

背景:耐甲氧西林和耐万古霉素的金黄色葡萄球菌是引起严重传染病的病原体,构成世界范围内真正的公共卫生威胁问题。在金黄色葡萄球菌中,最有效的耐多药系统是NorA外排泵。因此,确定外排泵抑制剂至关重要。

目的:在本文中,我们介绍了通过抑制金黄色葡萄球菌NorA外排泵来充当抗生素抗性调节剂的新型天然和合成化合物的更新。

结果:已鉴定出几种能够恢复抗生素活性的抗S型化合物。金黄色葡萄球菌菌株,充当NorA外排泵抑制剂。最有前途的化合物是喹啉,吲哚,吡啶,苯酚和含硫杂环。然而,这些化合物的高度结构多样性使得难以建立良好的结构活性相关性,从而使设计的化合物具有更广阔的前景和活性。

结论:尽管在寻找新的作为排泄泵抑制剂的抗生素佐剂方面付出了巨大的努力,并且尽管取得了令人鼓舞的结果,但目前尚无授权用于人或兽用或临床试验的排泄泵抑制剂。不幸的是,似乎自青霉素发现以来,感染控制策略一直保持不变,并且大多数努力仍集中在发现新型抗生素上,而不是试图延长可用抗生素的寿命,同时与细菌耐药性机制作斗争。

更新日期:2020-11-02
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