| 1. |
- Cegelski, Lynette, et al.
(författare)
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Small-molecule inhibitors target Escherichia coli amyloid biogenesis and biofilm formation
- 2009
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Ingår i: Nature Chemical Biology. - : Nature Publishing Group. - 1552-4450 .- 1552-4469. ; 5:12, s. 913-919
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Tidskriftsartikel (refereegranskat)abstract
- Curli are functional extracellular amyloid fibers produced by uropathogenic Escherichia coli (UPEC) and other Enterobacteriaceae. Ring-fused 2-pyridones, such as FN075 and BibC6, inhibited curli biogenesis in UPEC and prevented the in vitro polymerization of the major curli subunit protein CsgA. The curlicides FN075 and BibC6 share a common chemical lineage with other ring-fused 2-pyridones termed pilicides. Pilicides inhibit the assembly of type1pili, which are required for pathogenesis during urinary tract infection. Notably, the curlicides retained pilicide activities and inhibited both curli-dependent and type 1–dependent biofilms. Furthermore, pretreatment of UPEC with FN075 significantly attenuated virulence in a mouse model of urinary tract infection. Curli and type 1pili exhibited exclusive and independent roles in promoting UPEC biofilms, and curli provided a fitness advantage in vivo. Thus, the ability of FN075 to block the biogenesis of both curli and type 1pili endows unique anti-biofilm and anti-virulence activities on these compounds.
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| 2. |
- Chorell, Erik, 1980-, et al.
(författare)
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Diverse functionalization of Thiazolo ring-fused 2-Pyridones
- 2007
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Ingår i: Journal of Organic Chemistry. - Washington, DC 20036, USA : American Chemical Society. - 0022-3263 .- 1520-6904. ; 72:13, s. 4917-4924
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Tidskriftsartikel (refereegranskat)abstract
- Thiazolo ring-fused 2-pyridones have proven to be highly interesting scaffolds for the development of biologically active compounds. Many methods are today available to introduce a variety of substituents in the 2-pyridone part of the heterocycle. Herein we disclose how a diverse set of substituents can be introduced in the thiazolo ring, with possibilities to vary also the spatial arrangement of the substituents. A key intermediate is the oxidized framework 9 for which an effective synthesis is described. The thiazolo part of this system can be substituted either via conjugate additions, resulting in trans selectivity, or via microwave-assisted Heck couplings that result in unsaturated aryl-substituted analogues. The scaffold can also be lithiated followed by the addition of various electrophiles, which increases the diversification potential substantially, as exemplified with the introduction of halogens, alkyl, acyl, and amide substituents.
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| 3. |
- Pemberton, Nils, et al.
(författare)
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Microwave-assisted synthesis and functionalization of 2-pyridones, 2-quinolones and other ring-fused 2-pyridones
- 2006
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Ingår i: Microwave-assisted synthesis of hetreocycles. - Berlin, Heidelberg : Springer-Verlag. - 9783540309833 ; , s. 1-30
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- 2-pyridones are important heterocycles with great applicability in medicinal chemistry and this core structure can be found in compounds with various biological/medicinal applications. Here we show how microwave-assisted chemistry can be used to effectively synthesize and functionalize substituted monocyclic 2-pyridones, 2-quinolones and other ring-fused 2-pyridones. The chapter covers recent advancements in this field mainly describing methods developed with instruments specially designed for microwave-assisted organic synthesis (MAOS).
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| 4. |
- Åberg, Veronica, 1976-, et al.
(författare)
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Carboxylic acid isosteres improve the activity of ring-fused 2-pyridones that inhibit pilus biogenesis in E. coli
- 2008
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Ingår i: Bioorganic & Medicinal Chemistry Letters. - : Elsevier Ltd. - 0960-894X. ; 18:12, s. 3536-3540
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Tidskriftsartikel (refereegranskat)abstract
- Ring-fused 2-pyridones, termed pilicides, are small synthetic compounds that inhibit pilus assembly in uropathogenic Escherichia coli. Their biological activity is clearly dependent upon a carboxylic acid functionality. Here, we present the synthesis and biological evaluation of carboxylic acid isosteres, including, for example, tetrazoles, acyl sulfonamides, and hydroxamic acids of two lead 2-pyridones. Two independent biological evaluations show that acyl sulfonamides and tetrazoles significantly improve pilicide activity against uropathogenic E. coli.
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| 5. |
- Åberg, Veronica, 1976-, et al.
(författare)
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Microwave-assisted decarboxylation of bicyclic 2-pyridone scaffolds and identification of A beta-peptide aggregation inhibitors
- 2005
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Ingår i: Organic and biomolecular chemistry. - London, U.K. : Royal Society of Chemistry. - 1477-0520 .- 1477-0539. ; 3:15, s. 2817-2823
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Tidskriftsartikel (refereegranskat)abstract
- A reagent-free microwave-assisted decarboxylation procedure for carboxylic acid functionalized bicyclic 2-pyridones has been developed. This new method, based on microwave heating at 220 degrees C for 600 seconds in N-methyl pyrrolidone (NMP), proved to be practical and very efficient, resulting in decarboxylated 2-pyridones in near-quantitative yields. The decarboxylated products and the intermediate 2-pyridones in the form of carboxylic acid methyl esters and carboxylic acids were screened for their effect on A beta-peptide aggregation. Two out of the 21 2-pyridones described in this study inhibited amyloid formation of the Alzheimer A beta(1-40) peptide. The effect was seen even at a 4 : 1 ratio of 2-pyridone and monomeric A beta-peptide.
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