RESUMO
To supply the increasing demand of natural high potency sweeteners to reduce the calories in food and beverages, we have looked to steviol glycosides. In this work we report the bioconversion of rebaudioside A to rebaudioside I using a glucosyltransferase enzyme. This bioconversion reaction adds one sugar unit with a 1â3 linkage. We utilized 1D and 2D NMR spectroscopy (1H, 13C, COSY, HSQC-DEPT, HMBC, 1D TOCSY and NOESY) and mass spectral data to fully characterize rebaudioside I.
Assuntos
Diterpenos do Tipo Caurano/metabolismo , Bebidas , Alimentos , Glucosídeos/metabolismo , Glucosiltransferases/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas/métodos , Edulcorantes/metabolismoRESUMO
Indole signaling is one of the putative universal signaling networks in bacteria. We have investigated the use of desformylflustrabromine (dFBr) derivatives for the inhibition of biofilm formation through modulation of the indole-signaling network in Escherichia coli and Staphylococcus aureus . We have found dFBr derivatives that are 10-1000 times more active than indole itself, demonstrating that the flustramine family of indolic natural products represent a privileged scaffold for the design of molecules to control pathogenic bacterial behavior.
Assuntos
Escherichia coli/metabolismo , Hidrocarbonetos Bromados/metabolismo , Alcaloides Indólicos/metabolismo , Indóis/metabolismo , Transdução de Sinais , Staphylococcus aureus/metabolismoRESUMO
Anti-biofilm agents have been developed based upon the flustramine family of alkaloids isolated from Flustra foliacea. A Garg interrupted Fischer indolization reaction was employed to access a core pyrroloindoline scaffold that was subsequently employed to create a pyrroloindoline triazole amide library. Screening for the ability to modulate biofilm formation against strains of Gram-positive and Gram-negative bacteria identified several compounds with low micromolar, non-toxic IC(50) values.
Assuntos
Amidas/síntese química , Antibacterianos , Bactérias/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Alcaloides Indólicos/química , Indóis/síntese química , Pirróis/síntese química , Amidas/química , Amidas/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Indóis/química , Indóis/farmacologia , Concentração Inibidora 50 , Estrutura Molecular , Pirróis/química , Pirróis/farmacologia , Relação Quantitativa Estrutura-Atividade , Bibliotecas de Moléculas Pequenas/síntese química , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologiaRESUMO
The synthesis and biofilm inhibitory activity of a 30-member aryl amide 2-aminoimidazole library against the three biofilm forming Gram-negative bacteria Escherichia coli, Psuedomonas aeruginosa, and Acinetobacter baumannii is presented. The most active compound identified inhibits the formation of E. coli biofilms with an IC(50) of 5.2 microM and was observed to be non-toxic to planktonic growth, demonstrating that analogues based on an aryl framework are viable options as biofilm inhibitors within the 2-aminoimidazole family.
Assuntos
Antibacterianos/química , Biofilmes/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Imidazóis/farmacologia , Acinetobacter baumannii/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Imidazóis/química , Plâncton/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/síntese químicaRESUMO
Multidrug-resistant bacterial infections continue to be a rising global health concern. Herein is described the development of a class of novel 2-aminobenzimidazoles with antibiotic activity. These active 2-aminobenzimidazoles retain their antibiotic activity against several strains of multidrug-resistant Staphylococcus aureus and Acinetobacter baumannii when compared to susceptible strains.
Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/síntese química , Antibacterianos/farmacologia , Benzimidazóis/síntese química , Benzimidazóis/farmacologia , Farmacorresistência Bacteriana Múltipla , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Antibacterianos/química , Benzimidazóis/química , Testes de Sensibilidade Microbiana , Conformação Molecular , Bibliotecas de Moléculas Pequenas , Estereoisomerismo , Relação Estrutura-AtividadeRESUMO
Following our interest in new diterpene glycosides with better taste profiles than that of Rebaudioside M, we have recently isolated and characterized Rebaudioside IX-a novel steviol glycoside-from a commercially-supplied extract of Stevia rebaudiana Bertoni. This molecule contains a hexasaccharide group attached at C-13 of the central diterpene core, and contains three additional glucose units when compared with Rebaudioside M. Here we report the complete structure elucidation-based on extensive Nuclear Magnetic Resonance (NMR) analysis (1H, 13C, Correlation Spectroscopy (COSY), Heteronuclear Single Quantum Coherence-Distortionless Enhancement Polarization Transfer (HSQC-DEPT), Heteronuclear Multiple Bond Correlation (HMBC), 1D Total Correlation Spectroscopy (TOCSY), Nuclear Overhauser Effect Spectroscopy (NOESY)) and mass spectral data-of this novel diterpene glycoside with nine sugar moieties and containing a relatively rare 1ï 6 α-linked glycoside. A steviol glycoside bearing nine glucose units is unprecedented in the literature, and could have an impact on the natural sweetener catalog.
Assuntos
Diterpenos/química , Glicosídeos/química , Stevia/química , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Extratos Vegetais/químicaRESUMO
A natural sweetener, Rubusoside (1), subjected to extreme pH and temperature conditions, resulted in the isolation and structural elucidation of one novel rubusoside degradant (7), together with seven known degradants (2-6 and 8-9). ID and 2D NMR spectroscopy (1H, 13C, COSY, HSQC-DEPT, HMBC, and NOESY) and mass spectral data were used to fully characterize the degradant 7.
Assuntos
Diterpenos do Tipo Caurano/química , Glucosídeos/química , Concentração de Íons de Hidrogênio , Estrutura MolecularRESUMO
In a continued search for novel diterpenoid glycosides, we recently isolated and characterized a Rebaudioside M derivative with a hydroxyl group at position 15 in the central diterpene core from an extract of Stevia rebaudiana Bertoni. Here we report the complete structure elucidation of 15α-hydroxy-Rebaudioside M (2) on the basis of NMR (1H, 13C, COSY, HSQC-DEPT, HMBC, 1D TOCSY, NOESY) and mass spectral data. Steviol glycoside with a hydroxyl group at C-15 in the central diterpene core has not been previously reported.
Assuntos
Stevia/química , Diterpenos/química , Diterpenos/isolamento & purificação , Glicosídeos/química , Glicosídeos/isolamento & purificaçãoRESUMO
This work aims to review and showcase the unique properties of rebaudioside M as a natural non-caloric potential sweetener in food and beverage products. To determine the potential of rebaudioside M, isolated from Stevia rebaudiana Bertoni, as a high potency sweetener, we examined it with the Beidler Model. This model estimated that rebaudioside M is 200-350 times more potent than sucrose. Numerous sensory evaluations of rebaudioside M's taste attributes illustrated that this steviol glycoside possesses a clean, sweet taste with a slightly bitter or licorice aftertaste. The major reaction pathways in aqueous solutions (pH 2-8) for rebaudioside M are similar to rebaudioside A. Herein we demonstrate that rebaudioside M could be of great interest to the global food industry because it is well-suited for blending and is functional in a wide variety of food and beverage products.
RESUMO
We report the isolation and complete structure of an isomer of rebaudioside D, known as rebaudioside D2. This novel steviol glycoside was isolated from a bioconversion reaction of rebaudioside A to rebaudioside D. Rebaudioside D2 possesses a relatively rare 1 --> 6 sugar linkage, which was discovered by extensive analysis of NMR (1H, 13C, COSY, HSQC-DEPT, HMBC, 1D TOCSY and NOESY) and mass spectral data.
Assuntos
Diterpenos do Tipo Caurano/química , Glicosídeos/química , Extratos Vegetais/química , Stevia/química , Espectroscopia de Ressonância Magnética , Estrutura MolecularRESUMO
A minor product, rebaudioside M2 (2), from the bioconversion reaction of rebaudioside A (4) to rebaudioside D (3), was isolated and the complete structure of the novel steviol glycoside was determined. Rebaudioside M2 (2) is considered an isomer of rebaudioside M (1) and contains a relatively rare 1â6 sugar linkage. It was isolated and characterized with NMR (1H, 13C, COSY, HSQC-DEPT, HMBC, 1D-TOCSY, and NOESY) and mass spectral data. Additionally, we emphasize the importance of 1D and 2D NMR techniques when identifying complex steviol glycosides. Numerous NMR spectroscopy studies of rebaudioside M (1), rebaudioside D (3), and mixture of 1 and 3 led to the discovery that SG17 which was previously reported in literature, is a mixture of rebaudioside D (3), rebaudioside M (1), and possibly other related steviol glycosides.
Assuntos
Diterpenos do Tipo Caurano/química , Diterpenos do Tipo Caurano/isolamento & purificação , Diterpenos do Tipo Caurano/metabolismo , Stevia/química , Trissacarídeos/química , Trissacarídeos/isolamento & purificação , Biotransformação , Isomerismo , Espectroscopia de Ressonância Magnética , Especificidade da Espécie , Trissacarídeos/metabolismoRESUMO
Herein is described a method of accessing indole/triazole and benzothiophene/triazole analogues that selectively promote or inhibit biofilm formation by Gram-positive and Gram-negative bacteria. Structure/function studies revealed that the addition of a bromine atom at the 2-position of the indole/triazole scaffold altered activity against both Gram-negative and Gram-positive bacteria and could transform a biofilm inhibitor into a biofilm inducer. Isosteric replacement of the indole core by a benzothiophene significantly impaired anti-biofilm activity. A competition assay exposing Escherichia coli to the most potent biofilm inducer and an inhibitor of E. coli biofilm formation was performed. The inducer exhibited the ability to mute the effect of the anti-biofilm compound for this targeted bacterial population.
RESUMO
The already considerable global public health threat of multi-drug resistant Gram-negative bacteria has become even more of a concern following the emergence of New-Delhi metallo-ß-lactamase (NDM-1) producing strains of Klebsiella pneumoniae and other Gram-negative bacteria. As an alternative approach to the traditional development of new bactericidal entities, we have identified a 2-aminoimidazole derived small molecule that acts as an antibiotic adjuvant and is able to suppress resistance of a NDM-1 producing strain of K. pneumoniae to imipenem and meropenem, in addition to suppressing resistance of other ß-lactam non-susceptible K. pneumoniae strains. The small molecule is able to lower carbapenem minimum inhibitory concentrations by up to 16-fold while exhibiting little bactericidal activity itself.