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设计、合成及烷基喹喔啉-2(1H)-酮衍生物的评价作为抗分子,抑制生物膜形成 Sch3。

Design, Synthesis, and Evaluation of Alkyl-Quinoxalin-2(1)-One Derivatives as Anti- Molecules, Inhibiting Biofilm Formation in Sch3.

机构信息

Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional (ENCB-IPN), Departamento de Química Orgánica, Ciudad de México 11340, México.

Escuela Nacional de Ciencias Biológicas del Instituto Politécnico Nacional (ENCB-IPN), Laboratorio de Investigación Clínica y Ambiental, Departamento de Microbiología, Ciudad de México 11340, México.

出版信息

Molecules. 2018 Nov 24;23(12):3075. doi: 10.3390/molecules23123075.

Abstract

With the increasing antibiotic resistance of bacterial strains, alternative methods for infection control are in high demand. (QS) is the bacterial communication system based on small molecules. QS is enables bacterial biofilm formation and pathogenic development. The interruption of QS has become a target for drug discovery, but remains in the early experimental phase. In this study, we synthesized a set of six compounds based on a scaffold (alkyl-quinoxalin-2(1)-one), new in the anti-QS of Gram-negative bacteria Sch3. By quantifying biofilm formation, we were able to monitor the effect of these compounds from concentrations of 1 to 100 µM. Significant reduction in biofilm formation was achieved by 3-hexylylquinoxalin-2(1)-one (), 3-hexylylquinoxalin-2(1)-one-6-carboxylic acid (), and 3-heptylylquinoxalin-2(1)-one-6-carboxylic acid (), ranging from 11% to 59% inhibition of the biofilm. This pilot study contributes to the development of anti-QS compounds to overcome the clinical challenge of resistant bacteria strains.

摘要

随着细菌菌株对抗生素耐药性的增加,人们迫切需要替代感染控制方法。(QS)是基于小分子的细菌通讯系统。QS 能够促进细菌生物膜的形成和致病性的发展。中断 QS 已成为药物发现的目标,但仍处于早期实验阶段。在这项研究中,我们合成了一组基于支架(烷基-喹喔啉-2(1)-酮)的六种化合物,这在革兰氏阴性菌 Sch3 的抗 QS 中是新的。通过定量生物膜形成,我们能够从 1 到 100 μM 的浓度监测这些化合物的效果。3-己基喹喔啉-2(1)-酮()、3-己基喹喔啉-2(1)-酮-6-羧酸()和 3-庚基喹喔啉-2(1)-酮-6-羧酸()对生物膜形成的抑制作用显著,抑制率为 11%至 59%。这项初步研究为开发抗 QS 化合物以克服耐药菌菌株的临床挑战做出了贡献。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92ed/6321446/ff9eb5495434/molecules-23-03075-sch001.jpg

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