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合成含环状二硫键的新型头孢菌素衍生物及其抗菌评价。

Synthesis and Antimicrobial Evaluation of New Cephalosporin Derivatives Containing Cyclic Disulfide Moieties.

机构信息

Department of Chemistry, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland.

出版信息

ACS Infect Dis. 2022 Nov 11;8(11):2327-2338. doi: 10.1021/acsinfecdis.2c00393. Epub 2022 Oct 17.

Abstract

Due to a steady increase in microbial resistance, there is a need to increase the effectiveness of antibiotic performance by involving additional mechanisms of their penetration or retention for their better action. Cephalosporins are a successful group of antibiotics to combat pathogenic microorganisms, including drug-resistant strains. In this study, we investigated the effect of newly synthesized cephalosporin derivatives with cyclic disulfide modifications against several Gram-positive and Gram-negative strains as well as against biofilm formation. The incorporation of asparagusic acid was found to be effective in improving the activity of the drug against Gram-negative strains compared to the all carbon-control compounds. Furthermore, we could demonstrate the successful reduction of biofilm formation for and at similar concentrations as obtained against planktonic cells. We propose that the incorporation of cyclic disulfides is one additional strategy to improve antibiotic activity and to combat bacterial infections.

摘要

由于微生物耐药性的稳步增加,需要通过增加抗生素穿透或保留的额外机制来提高其疗效,以实现更好的作用。头孢菌素是一组成功的抗生素,可对抗包括耐药菌株在内的致病微生物。在这项研究中,我们研究了新合成的带有环状二硫键修饰的头孢菌素衍生物对几种革兰氏阳性和革兰氏阴性菌株以及对抗生物膜形成的影响。与全碳对照化合物相比,发现天门冬氨酸的掺入可有效提高药物对革兰氏阴性菌株的活性。此外,我们能够证明在类似浓度下成功减少了 和 对浮游细胞的生物膜形成。我们提出,环状二硫键的掺入是提高抗生素活性和对抗细菌感染的另一种策略。

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