Inhibitors of the acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridylyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU). Part 2: Optimization of physical properties leading to antibacterial aryl sulfonamides

Stokes, Suzanne S.; Albert, Robert; Buurman, Ed T.; Andrews, Beth; Shapiro, Adam B.; Green, Oluyinka M.; McKenzie, Andrew R.; Otterbein, Ludovic R.

doi:10.1016/j.bmcl.2012.10.003

Cited by 79 publications

(41 citation statements)

References 14 publications

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“…10 Multiple screening strategies also led to the discovery of novel E. coli GlmU inhibitors, including arylamines 11 and aryl sulfonamides. 6,12,13 Recently, an in silico screening strategy using ligand-guided and structure-guided techniques led to the identification of two promising sulfonamide inhibitors. 14 Terreic acid is a reported antibacterial inhibitor, but its cellular and molecular targets are still unknown.…”

Section: Introductionmentioning

confidence: 99%

Escherichia coli N-Acetylglucosamine-1-Phosphate-Uridyltransferase/Glucosamine-1-Phosphate-Acetyltransferase (GlmU) Inhibitory Activity of Terreic Acid Isolated from Aspergillus terreus

et al. 2016

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Secondary metabolite of Aspergillus terreus, terreic acid, is a reported potent antibacterial that was identified more than 60 years ago, but its cellular target(s) are still unknown. Here we screen its activity against the acetyltransferase domain of a bifunctional enzyme, Escherichia coli N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU). An absorbance-based assay was used to screen terreic acid against the acetyltransferase activity of E. coli GlmU. Terreic acid was found to inhibit the acetyltransferase domain of E. coli GlmU with an IC 50 of 44.24 ± 1.85 µM. Mode of inhibition studies revealed that terreic acid was competitive with AcCoA and uncompetitive with GlcN-1-P. It also exhibited concentration-dependent killing of E. coli ATCC 25922 up to 4× minimum inhibitory concentration and inhibited the growth of biofilms generated by E. coli. Characterization of resistant mutants established mutation in the acetyltransferase domain of GlmU. Terreic acid was also found to be metabolically stable in the in vitro incubations with rat liver microsome in the presence of a NADPH regenerating system. The studies reported here suggest that terreic acid is a potent antimicrobial agent and support that E. coli GlmU acetyltransferase is a molecular target of terreic acid, resulting in its antibacterial activity.

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Section: Introductionmentioning

confidence: 99%

Escherichia coli N-Acetylglucosamine-1-Phosphate-Uridyltransferase/Glucosamine-1-Phosphate-Acetyltransferase (GlmU) Inhibitory Activity of Terreic Acid Isolated from Aspergillus terreus

et al. 2016

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“…Sulfonamides were the principally remedies fundamentally engaged and progressively castoff for petition and chemotherapeutic vehicles intimidating to an variety of maladies [1]. More than thirty drugs obligating this functionality are in assessable apply, entering antiseptic [2,3], and extra biological activities [4][5][6][7][8].…”

Section: Discussionmentioning

confidence: 99%

Crystal structure of the co-crystalline adduct 4-((4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino)-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide - acetic acid (1/1), C₂₁H₂₄N₄O₄S ⋅ C₂H₄O₂

Ghorab

Alsaid

Al-Dosari

et al. 2017

Zeitschrift Für Kristallographie - New Crystal Structures

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C 23 H 28 N4O 6 S, triclinic, P1 (no. 2), a = 7.3612(3) Å, CCDC no.: 1468856The asymmetric unit of the title crystal structure is shown in the figure. Tables 1 and 2 contain details on crystal structure and measurement conditions and a list of the atoms including atomic coordinates and displacement parameters. Source of material2-((Dimethylamino)methylene)-5,5-dimethylcyclohexane-1,3-dione (1.95 g, 0.01 mol) and 4-amino-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide (2.78 g, 0.01 mol) was added

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“…Cytotoxicity of sample = (1-Experimental well abs/ abs of negative control) x100. 3 were also recorded at 38.65, 60.21 ppm and 50.39, 63.99, respectively. The cheMICal shift value of -OCH 3 was observed on downfield side than -NCH 3 due to strong electron withdrawing influence of oxygen than nitrogen.…”

Section: Antioxidant Activitymentioning

confidence: 93%

“…More than 30 drugs having sulfa drug as a functional group are in clinical use, such as antibacterial [2], antifungal [3], antiprotozoal [4], anti-inflammatory [5], and translational initiation inhibitors [6]. More recent use of sulfonamides are as an anticancer agent [7], antiviral HIV [8], and in Alzheimer's disease [9].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and characterization of novel sulfonamides derivatives and their antimicrobial, antioxidant and cytotoxicity evaluation

Rehman¹,

Qadir²,

Ali³

et al. 2018

Bull. Chem. Soc. Eth.

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ABSTRACT. Five novel sulfonamides derivatives HR5-HR8 and HR14 were synthesized by sulfonylation of primary or secondary amine in the presence of base through nucleophilic substitution reaction. Structural elucidation was carried out through FT-IR, UV, 1 H NMR, MS and elemental analysis. Prepared compounds were evaluated against pathogenic strains of bacteria (S. aureus and E. coli) and fungi (A. flavous and A. nyger). Results were compared against standard antifungal and bacterial drug already available in market (isoconazole and sulfmethoxazole). It was found that compound HR14 showed good activity with MIC 1.5 µg/mL and 2.0 µg/mL for S. aurues and E. coli, respectively. While HR5 showed best antifungal activity with zone of inhibition 27.2+0.12 mm (MIC: 5.25 µg/mL) and 18.1+0.12 mm (MIC: 12.5 µg/mL) against A. flavous and A. nyger, respectively. Synthesized compounds were also tested for their in vitro antioxidant activity by using DDPH. Amongst all compounds HR5 was found to have potential activity with 15.60% antioxidant activity at 6 mM concentration.

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Inhibitors of the acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridylyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU). Part 2: Optimization of physical properties leading to antibacterial aryl sulfonamides

Cited by 79 publications

References 14 publications

Escherichia coli N-Acetylglucosamine-1-Phosphate-Uridyltransferase/Glucosamine-1-Phosphate-Acetyltransferase (GlmU) Inhibitory Activity of Terreic Acid Isolated from Aspergillus terreus

Escherichia coli N-Acetylglucosamine-1-Phosphate-Uridyltransferase/Glucosamine-1-Phosphate-Acetyltransferase (GlmU) Inhibitory Activity of Terreic Acid Isolated from Aspergillus terreus

Crystal structure of the co-crystalline adduct 4-((4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino)-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide - acetic acid (1/1), C₂₁H₂₄N₄O₄S ⋅ C₂H₄O₂

Synthesis and characterization of novel sulfonamides derivatives and their antimicrobial, antioxidant and cytotoxicity evaluation

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Inhibitors of the acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridylyltransferase/glucosamine-1-phosphate-acetyltransferase (GlmU). Part 2: Optimization of physical properties leading to antibacterial aryl sulfonamides

Cited by 79 publications

References 14 publications

Escherichia coli N-Acetylglucosamine-1-Phosphate-Uridyltransferase/Glucosamine-1-Phosphate-Acetyltransferase (GlmU) Inhibitory Activity of Terreic Acid Isolated from Aspergillus terreus

Escherichia coli N-Acetylglucosamine-1-Phosphate-Uridyltransferase/Glucosamine-1-Phosphate-Acetyltransferase (GlmU) Inhibitory Activity of Terreic Acid Isolated from Aspergillus terreus

Crystal structure of the co-crystalline adduct 4-((4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino)-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide - acetic acid (1/1), C21H24N4O4S ⋅ C2H4O2

Synthesis and characterization of novel sulfonamides derivatives and their antimicrobial, antioxidant and cytotoxicity evaluation

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Crystal structure of the co-crystalline adduct 4-((4,4-dimethyl-2,6-dioxocyclohexylidene)methylamino)-N-(4,6-dimethylpyrimidin-2-yl)benzenesulfonamide - acetic acid (1/1), C₂₁H₂₄N₄O₄S ⋅ C₂H₄O₂