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硒化合物作为新型抗菌剂和细菌外排泵抑制剂。

Selenocompounds as Novel Antibacterial Agents and Bacterial Efflux Pump Inhibitors.

机构信息

Department of Medical Microbiology and Immunobiology, Faculty of Medicine, University of Szeged, Dóm tér 10, 6720 Szeged, Hungary.

Department of Obstetrics and Gynecology, Faculty of Medicine, University of Szeged, Semmelweis utca 1, 6725 Szeged, Hungary.

出版信息

Molecules. 2019 Apr 16;24(8):1487. doi: 10.3390/molecules24081487.

Abstract

Bacterial multidrug resistance is becoming a growing problem for public health, due to the development and spreading of bacterial strains resistant to antimicrobials. In this study, the antibacterial and multidrug resistance reversing activity of a series of seleno-carbonyl compounds has been evaluated. The effects of eleven selenocompounds on bacterial growth were evaluated in , methicillin resistant (MRSA), , and D. The combination effect of compounds with antibiotics was examined by the minimum inhibitory concentration reduction assay. Their efflux pump (EP) inhibitory properties were assessed using real-time fluorimetry. Relative expressions of EP and quorum-sensing genes were studied by quantitative PCR. Results showed that a methylketone selenoester had remarkable antibacterial activity against Gram-positive bacteria and potentiated the activity of oxacillin in MRSA. Most of the selenocompounds showed significant anti-chlamydial effects. The selenoanhydride and the diselenodiester were active inhibitors of the AcrAB-TolC system. Based on these results it can be concluded that this group of selenocompounds can be attractive potential antibacterials and EP inhibitors. The discovery of new derivatives with a significant antibacterial activity as novel selenocompounds, is of high impact in the fight against resistant pathogens.

摘要

细菌的多药耐药性正在成为公共卫生的一个日益严重的问题,这是由于对抗生素具有耐药性的细菌菌株的发展和传播所致。在这项研究中,评估了一系列硒羰基化合物的抗菌和多药耐药性逆转活性。在 、耐甲氧西林金黄色葡萄球菌 (MRSA) 、 和 D 中评估了 11 种硒化合物对细菌生长的影响。通过最小抑菌浓度降低测定法检查了化合物与抗生素的组合效果。使用实时荧光法评估了它们的外排泵 (EP) 抑制特性。通过定量 PCR 研究了 EP 和群体感应基因的相对表达。结果表明,一种甲基酮硒酸酯对革兰氏阳性菌具有显著的抗菌活性,并增强了 MRSA 中苯唑西林的活性。大多数硒化合物对衣原体表现出显著的抑制作用。硒酐和二硒二酯是 AcrAB-TolC 系统的有效抑制剂。基于这些结果可以得出结论,该组硒化合物可以作为有吸引力的潜在抗菌和 EP 抑制剂。作为新型硒化合物,发现具有显著抗菌活性的新衍生物对抗耐药病原体具有重要意义。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/828e/6514980/a9f1236341ad/molecules-24-01487-g001.jpg

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