羰基丙烯酸衍生物及其破坏生物膜形成的能力

IF 0.6 4区 综合性期刊 Q3 MULTIDISCIPLINARY SCIENCES
Pattarapon Pumirat, Thunchanok Tansutat, Chutima Jiarpinitnun
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引用次数: 0

摘要

细菌对抗生素的耐药性的迅速出现极大地推动了对新疗法的需求。细菌用来增强对抗生素耐药性的策略之一是将自己嵌入被称为生物膜的聚合基质中。处于生物膜状态的细菌对抗生素和免疫反应具有高度耐药性,因此更难以根除。因此,抗生素薄膜剂被认为是解决细菌抗生素耐药性问题的一种替代策略。我们的实验室专注于细菌的交流过程,称为群体感应(QS),这是细菌进行生物膜等群体行为的关键。LasR的半胱氨酸残基是QS蛋白的关键调节因子,在QS介导的生物膜形成中起重要作用。此外,含有半胱氨酸的生物分子与细菌的发病机制有关。在此,我们探索了硫醇反应分子干扰致病性革兰氏阴性铜绿假单胞菌(P. aeruginosa)生物膜形成的能力。我们推测,巯基活性分子可能与关键的QS酶半胱氨酸残基或含半胱氨酸的生物分子的巯基发生反应,从而导致病原体形成生物膜的能力降低。羰基丙烯酸化合物在生理条件下与含半胱氨酸的蛋白质迅速发生巯基-迈克尔反应。合成了三种新的羰基丙烯酸衍生物,并对它们的抗生物膜活性进行了测试。所有合成的化合物都能以浓度依赖的方式抑制生物膜的形成,对细菌没有毒性。衍生物1a表现出最强的抗菌膜活性,IC50为85 μM。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Carbonylacrylic Derivatives and Their Ability to Disrupt Biofi lm Formation
The rapid emergence of bacterial resistance to antibiotics has greatly pressed the need for novel therapeutics. One of the strategies bacteria use to enhance their resistance toward antibiotics is to embed themselves into polymeric matrices known as a biofi lm. Bacteria in a biofi lm state are highly resistant towards antibiotics and immune response, thereby more diffi cult to eradicate. Hence, antibiofi lm agents are considered an alternative strategy to unravel problems regarding bacterial antibiotic resistance. Our lab has focused on bacterial communication process called quorum sensing (QS), which is crucial for bacteria to conduct group behaviors such as biofi lm. Cysteine residue of LasR, key QS protein regulator, has been suggested to play an important role in QS-mediated biofi lm formation. In addition, cysteine-containing biomolecules have been implicated in bacterial pathogenesis. Herein, we explored the ability of thiol-reactive molecules for their ability to interfere with biofi lm formation in pathogenic Gram-negative Pseudomonas aeruginosa (P. aeruginosa). We hypothesized that the thiol-reactive molecules could potentially react with sulfhydryl group of cysteine residue of crucial QS enzyme or of cysteine-containing biomolecules that may lead to the reduce in the ability of the pathogen to form biofi lm. Carbonylacrylic compounds were previously reported to rapidly undergo thiol-Michael reaction with cysteine-containing proteins under physiological conditions. Total of three new carbonylacrylic derivatives were synthesized and tested for their anti-biofi lm activity. All synthesized compounds could inhibit biofi lm formation in a concentration-dependent manner without toxicity to bacteria. Derivative 1a exhibited the most potent antibiofi lm activity with IC50 of 85 μM.
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来源期刊
Chiang Mai Journal of Science
Chiang Mai Journal of Science MULTIDISCIPLINARY SCIENCES-
CiteScore
1.00
自引率
25.00%
发文量
103
审稿时长
3 months
期刊介绍: The Chiang Mai Journal of Science is an international English language peer-reviewed journal which is published in open access electronic format 6 times a year in January, March, May, July, September and November by the Faculty of Science, Chiang Mai University. Manuscripts in most areas of science are welcomed except in areas such as agriculture, engineering and medical science which are outside the scope of the Journal. Currently, we focus on manuscripts in biology, chemistry, physics, materials science and environmental science. Papers in mathematics statistics and computer science are also included but should be of an applied nature rather than purely theoretical. Manuscripts describing experiments on humans or animals are required to provide proof that all experiments have been carried out according to the ethical regulations of the respective institutional and/or governmental authorities and this should be clearly stated in the manuscript itself. The Editor reserves the right to reject manuscripts that fail to do so.
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