2-heptyl-3-hydroxy-4(1H)-Quinolone
(Synonyms: 2-庚基-3-羟基-4(1H)-喹啉酮,PQS, Pseudomonas Quinolone Signal) 目录号 : GC45912
A bacterial quorum-sensing signaling molecule
Cas No.:108985-27-9
Sample solution is provided at 25 µL, 10mM.
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2-heptyl-3-hydroxy-4(1H)-Quinolone is a quorum-sensing signaling molecule produced by P. aeruginosa in response to increasing cell density.[1] It increases expression of the lasB gene, which encodes the virulence factor elastase, in P. aeruginosa (EC50 = ~30 µM in a reporter cell assay). 2-heptyl-3-hydroxy-4(1H)-Quinolone (60 µM) increases secretion of the metabolite pyocyanin and the lectin PA-IL, as well as increases biofilm production in P. aeruginosa populations.[2] It also reduces iron levels in P. aeruginosa growth media when used at a concentration of 40 µM and acts as an iron chelator in a Fe(III)-sulfate solution.[3]
Reference:
[1]. Pesci, E.C., Milbank, J.B.J., Pearson, J.P., et al. Quinolone signaling in the cell-to-cell communication system of Pseudomonas aeruginosa. Proc. Natl. Acad. Sci. USA 96(20), 11229-11234 (1999).
[2]. Diggle, S.P., Winzer, K., Chhabra, S.R., et al. The Pseudomonas aeruginosa quinolone signal molecule overcomes the cell density-dependency of the quorum sensing hierarchy, regulates rhl-dependent genes at the onset of stationary phase and can be produced in the absence of LasR. Mol. Microbiol. 50(1), 29-43 (2003).
[3]. Bredenbruch, F., Geffers, R., Nimtz, M., et al. The Pseudomonas aeruginosa quinolone signal (PQS) has an iron-chelating activity. Environ. Microbiol. 8(8), 1318-1329 (2006).
| Cas No. | 108985-27-9 | SDF | |
| 别名 | 2-庚基-3-羟基-4(1H)-喹啉酮,PQS, Pseudomonas Quinolone Signal | ||
| 化学名 | 2-heptyl-3-hydroxy-4(1H)-quinolinone | ||
| Canonical SMILES | OC1=C(CCCCCCC)NC2=CC=CC=C2C1=O | ||
| 分子式 | C16H21NO2 | 分子量 | 259.3 |
| 溶解度 | Soluble in methanol | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.8565 mL | 19.2827 mL | 38.5654 mL |
| 5 mM | 0.7713 mL | 3.8565 mL | 7.7131 mL |
| 10 mM | 0.3857 mL | 1.9283 mL | 3.8565 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Neuroprotective effects of 2-heptyl-3-hydroxy-4-quinolone in HT22 mouse hippocampal neuronal cells
Bioorg Med Chem Lett 2021 Oct 1;49:128312.PMID:34375718DOI:10.1016/j.bmcl.2021.128312.
The neuroprotective activity of 2-heptyl-3-hydroxy-4(1H)-Quinolone (compound 1) was evaluated using the neurotoxicity of glutamate in the HT22 cell line. Compound 1, known as a signal molecule of the bacterial quorum-sensing system, protects neuronal cells from glutamate-induced neurotoxicity by inhibiting cellular Ca2+ uptake and glutamate-triggered ROS accumulation. MAPK signaling pathway inhibition by compound 1 was evaluated by immunoblotting the phosphorylation status of the proteins. Furthermore, pro-apoptotic protein levels and AIF translocation to the nucleus were found to be reduced by compound 1. In conclusion, compound 1 showed neuroprotective effects by inhibiting apoptotic neuronal cell death.
Novel 2-Substituted 3-Hydroxy-1,6-dimethylpyridin-4(1 H)-ones as Dual-Acting Biofilm Inhibitors of Pseudomonas aeruginosa
J Med Chem 2020 Oct 8;63(19):10921-10945.PMID:32866008DOI:10.1021/acs.jmedchem.0c00763.
2-heptyl-3-hydroxy-4(1H)-Quinolone (PQS), a compound from P. aeruginosa, functions as both a quorum sensing (QS) regulator and a potent iron chelator to induce expression of pyoverdine and pyochelin which are involved in high-affinity iron transport systems. A potential dual-acting antibiofilm strategy requires molecules designed to interfere with iron uptake and the QS system of P. aeruginosa. A series of 2-substituted 3-hydroxy-1,6-dimethylpyridin-4-ones have been designed, synthesized, and tested as biofilm inhibitors of P. aeruginosa. One compound, N-((1,3,6-trimethyl-4-oxo-1,4-dihydropyridin-2-yl)methyl)hexanamide (10d), exhibits 68.67% biofilm inhibitory activity at 20 μM. Further mechanistic studies have confirmed that this compound not only inhibits the QS systems of P. aeruginosa but also acts as an iron chelator to compete strongly with pyoverdine, causing iron deficiency in bacteria. The pyoverdine receptor FpvA was revealed as the target of 10d by the Pvds mutant strain, fpvA-overexpressed strain, and in silico studies.
The Alkylquinolone Repertoire of Pseudomonas aeruginosa is Linked to Structural Flexibility of the FabH-like 2-heptyl-3-hydroxy-4(1H)-Quinolone (PQS) Biosynthesis Enzyme PqsBC
Chembiochem 2018 Jul 16;19(14):1531-1544.PMID:29722462DOI:10.1002/cbic.201800153.
Pseudomonas aeruginosa is a bacterial pathogen that causes life-threatening infections in immunocompromised patients. It produces a large armory of saturated and mono-unsaturated 2-alkyl-4(1H)-quinolones (AQs) and AQ N-oxides (AQNOs) that serve as signaling molecules to control the production of virulence factors and that are involved in membrane vesicle formation and iron chelation; furthermore, they also have, for example, antibiotic properties. It has been shown that the β-ketoacyl-acyl-carrier protein synthase III (FabH)-like heterodimeric enzyme PqsBC catalyzes the last step in the biosynthesis of the most abundant AQ congener, 2-heptyl-4(1H)-quinolone (HHQ), by condensing octanoyl-coenzyme A (CoA) with 2-aminobenzoylacetate (2-ABA), but the basis for the large number of other AQs/AQNOs produced by P. aeruginosa is not known. Here, we demonstrate that PqsBC uses different medium-chain acyl-CoAs to produce various saturated AQs/AQNOs and that it also biosynthesizes mono-unsaturated congeners. Further, we determined the structures of PqsBC in four different crystal forms at 1.5 to 2.7 Å resolution. Together with a previous report, the data reveal that PqsBC adopts open, intermediate, and closed conformations that alter the shape of the acyl-binding cavity and explain the promiscuity of PqsBC. The different conformations also allow us to propose a model for structural transitions that accompany the catalytic cycle of PqsBC that might have broader implications for other FabH-enzymes, for which such structural transitions have been postulated but have never been observed.
Microwave-assisted preparation of the quorum-sensing molecule 2-heptyl-3-hydroxy-4(1H)-Quinolone and structurally related analogs
Nat Protoc 2012 May 24;7(6):1184-92.PMID:22635110DOI:10.1038/nprot.2012.054.
An optimized procedure for the efficient preparation of 2-heptyl-3-hydroxy-4(1H)-Quinolone (Pseudomonas quinolone signal or PQS) and a diverse range of structurally related 2-alkyl-4-quinolones with biological activity is presented. The two-step synthesis begins with the formation of α-chloro ketones by the coupling of a Weinreb amide (2-chloro-N-methoxy-N-methylacetamide) and an appropriate Grignard reagent. The resulting α-chloro ketones can be reacted with commercially available anthranilic acids under microwave irradiation conditions to furnish the desired 2-alkyl-4-quinolone products. As a typical example, the synthesis of PQS, a molecule involved in quorum sensing in the pathogenic bacterium Pseudomonas aeruginosa, is described in detail. The first step of this process (α-chloro ketone formation) takes ∼10 h in total to complete from commercially available bromoheptane and 2-chloro-N-methoxy-N-methylacetamide. The second step (microwave-assisted reaction with anthranilic acid) takes ∼14 h in total to complete (the reaction typically proceeds in ∼30 min, with work-up and purification requiring ∼13 h).
Gut Microbiota Protected Against pseudomonas aeruginosa Pneumonia via Restoring Treg/Th17 Balance and Metabolism
Front Cell Infect Microbiol 2022 Jun 16;12:856633.PMID:35782123DOI:10.3389/fcimb.2022.856633.
Backgrounds and purpose: The theory of "entero-pulmonary axis" proves that pneumonia leads to gut microbiota disturbance and Treg/Th17 immune imbalance. This study is aimed to explore the potential mechanism of fecal microbiota transplantation (FMT) in the treatment of Pseudomonas aeruginosa pneumonia, in order to provide new insights into the treatment of pneumonia. Methods: Pseudomonas aeruginosa and C57/BL6 mice were used to construct the acute pneumonia mouse model, and FMT was treated. Histopathological changes in lung and spleen were observed by HE staining. The expression of CD25, Foxp3 and IL-17 was observed by immunofluorescence. The proportion of Treg and Th17 cells was analyzed by flow cytometry. Serum IL-6, LPS, and IFN-γ levels were detected by ELISA. The expression of TNF-α, IFN-γ, IL-6, IL-2, Foxp3, IL-17, IL-10, and TGFβ1 in lung tissue homogenate was detected by qRT-PCR. 16S rRNA sequencing and non-targeted metabolomics were used to analyze gut microbiota and metabolism. Results: Pseudomonas aeruginosa caused the decrease of body weight, food and water intake, lung tissue, and spleen injury in mice with pneumonia. Meanwhile, it caused lung tissue and serum inflammation, and Treg/Th17 cell imbalance in mice with pneumonia. Pseudomonas aeruginosa reduced the diversity and number of gut microbiota in pneumonia mice, resulting in metabolic disorders, superpathway of quinolone and alkylquinolone biosynthesis. It also led to the decrease of 2-heptyl-3-hydroxy-4(1H)-Quinolone biosynthesis, and the enrichment of Amino sugar and nucleotide sugar metabolism. FMT with or without antibiotic intervention restored gut microbiota abundance and diversity, suppressed inflammation and tissue damage, and promoted an immunological balance of Treg/Th17 cells in mice with pneumonia. In addition, FMT inhibited the aerobactin biosynthesis, 4-hydroxyphenylacetate degradation, superpathway of lipopolysaccharide biosynthesis and L-arabinose degradation IV function of microbiota, and improved amino sugar and nucleotide sugar metabolism. Conclusions: FMT restored the Treg/Th17 cells' balance and improved inflammation and lung injury in mice with Pseudomonas aeruginosa pneumonia by regulating gut microbiota disturbance and metabolic disorder.