Synthesis and antimicrobial activity of 6-sulfo-6-deoxy-D-glucosamine and its derivatives

Skarbek, Kornelia; Gabriel, Iwona; Szweda, Piotr; Wojciechowski, Marek; Khan, Muna A.; Görke, Boris; Milewski, Sławomir; Milewska, Maria J.

doi:10.1016/j.carres.2017.06.002

Cited by 6 publications

(9 citation statements)

References 36 publications

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“…The same group also reported GlcN6S ( 117 , Figure A), its N -acetyl ( 118 ) and methyl ester derivatives, ADGS ( 119 ) and NAcADGS ( 120 ) as inhibitors of GlcN-6-P synthase . A SAR study revealed that methyl sulfonate derivatives were inactive against fungi (MIC > 4.0 mg/mL).…”

Section: Antifungals Targeting the Cell Wallmentioning

confidence: 87%

“…The same group also reported GlcN6S (117, Figure 28A), its N-acetyl (118) and methyl ester derivatives, ADGS (119) and NAcADGS (120) as inhibitors of GlcN-6-P synthase. 190 A SAR study revealed that methyl sulfonate derivatives were inactive against fungi (MIC > 4.0 mg/mL). Other derivatives such as GlcN6S, ADGS, and NAcADGS displayed improved antifungal activity with MIC values of 1 mg/mL.…”

Section: Antifungals Targeting the Cell Wallmentioning

confidence: 99%

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Recent Progress in the Discovery of Antifungal Agents Targeting the Cell Wall

2020

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Due to the limit of available treatments and the emergence of drug resistance in the clinic, invasive fungal infections are an intractable problem with high morbidity and mortality. The cell wall, as a fungi-specific structure, is an appealing target for the discovery and development of novel and low-toxic antifungal agents. In an attempt to accelerate the discovery of novel cell wall targeted drugs, this Perspective will provide a comprehensive review of the progress made to date on the development of fungal cell wall inhibitors. Specifically, this review will focus on the targets, discovery process, chemical structures, antifungal activities, and structure–activity relationships. Although two types of cell wall antifungal agents are clinically available or in clinical trials, it is still a long way for the other cell wall targeted inhibitors to be translated into clinical applications. Future efforts should be focused on the identification of inhibitors against novel conserved cell wall targets.

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Section: Antifungals Targeting the Cell Wallmentioning

confidence: 87%

Section: Antifungals Targeting the Cell Wallmentioning

confidence: 99%

Recent Progress in the Discovery of Antifungal Agents Targeting the Cell Wall

2020

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“…Indeed, 2‐amino‐2‐deoxy‐ d ‐glucitol‐6‐phosphate (ADGP) (Compound 13 ) inhibits E. coli GlmS (K i = 25 μM); however, it possesses poor antibacterial activity due to low uptake by microbial cells (Figure 4). 48 Analogues of ADGP have also been examined (Compounds 14–19 ) against the E. coli enzyme, although potency greatly varies among these compounds, and they lack whole cell activity against both Gram‐positive and Gram‐negative bacteria 49,50 . Another class of analogue inhibitors include those of the reaction product, GlcN‐6‐P.…”

Section: Glucosamine‐6‐phosphate Synthase (Glms)mentioning

confidence: 99%

“…Moreover, a common problem encountered across the inhibitors for GlmS, GlmM, and GlmU is a lack of activity against whole organisms. Whilst some inhibitors demonstrate micromolar potency, they are unable to penetrate bacterial cells to exert their activity 49,93,95,96 . The challenge is, therefore, to develop compounds that, while retaining their affinities for their respective targets, can cross the cytoplasmic membrane.…”

Section: The Future Of Udp‐glcnac In Antibiotic Developmentmentioning

confidence: 99%

Biosynthesis of uridine diphosphate N‐Acetylglucosamine: An underexploited pathway in the search for novel antibiotics?

et al. 2022

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Although the prevalence of antibiotic resistance is increasing at an alarming rate, there are a dwindling number of effective antibiotics available. Thus, the development of novel antibacterial agents should be of utmost importance. Peptidoglycan biosynthesis has been and is still an attractive source for antibiotic targets; however, there are several components that remain underexploited. In this review, we examine the enzymes involved in the biosynthesis of one such component, UDP‐N‐acetylglucosamine, an essential building block and precursor of bacterial peptidoglycan. Furthermore, given the presence of a similar biosynthesis pathway in eukaryotes, we discuss the current knowledge on the differences and similarities between the bacterial and eukaryotic enzymes. Finally, this review also summarises the recent advances made in the development of inhibitors targeting the bacterial enzymes.

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“… The hypothetical complex of RO0509347 with human GlcN-6-P synthase. Drawing based on the results of docking calculations to the hGFAT2 matrix (pdbid: 6r4f) 123 , performed with the use of Autodock 4.2, according to the procedure described previously 124 . A single subunit of the tetrameric enzyme is shown, with GAH and ISOM active centres indicated as red and green spheres respectively.…”

Section: Inhibitors Binding Outside the Active Centres Of Glcn-6-p Sy...mentioning

confidence: 99%

Inhibitors of glucosamine-6-phosphate synthase as potential antimicrobials or antidiabetics – synthesis and properties

Stefaniak

Nowak

Wojciechowski

et al. 2022

Journal of Enzyme Inhibition and Medicinal Chemistry

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Glucosamine-6-phosphate synthase (GlcN-6-P synthase) is known as a promising target for antimicrobial agents and antidiabetics. Several compounds of natural or synthetic origin have been identified as inhibitors of this enzyme. This set comprises highly selective l -glutamine, amino sugar phosphate or transition state intermediate cis -enolamine analogues. Relatively low antimicrobial activity of these inhibitors, poorly penetrating microbial cell membranes, has been improved using the pro-drug approach. On the other hand, a number of heterocyclic and polycyclic compounds demonstrating antimicrobial activity have been presented as putative inhibitors of the enzyme, based on the results of molecular docking to GlcN-6-P synthase matrix. The most active compounds of this group could be considered promising leads for development of novel antimicrobial drugs or antidiabetics, provided their selective toxicity is confirmed.

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Synthesis and antimicrobial activity of 6-sulfo-6-deoxy-D-glucosamine and its derivatives

Cited by 6 publications

References 36 publications

Recent Progress in the Discovery of Antifungal Agents Targeting the Cell Wall

Recent Progress in the Discovery of Antifungal Agents Targeting the Cell Wall

Biosynthesis of uridine diphosphate N‐Acetylglucosamine: An underexploited pathway in the search for novel antibiotics?

Inhibitors of glucosamine-6-phosphate synthase as potential antimicrobials or antidiabetics – synthesis and properties

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