Enzyme Inhibition by Quinones

Hoffmann‐Ostenhof, O.

doi:10.1016/b978-0-12-395623-1.50013-7

Cited by 22 publications

(5 citation statements)

References 48 publications

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“…Quinones are essential lipid electron carriers of the aerobic and anaerobic respiratory chain in bacteria ( e.g. , ubiquinone and menaquinone) (31, 39, 71). However, many natural antimicrobial compounds contain quinone-like structures that are encountered as exogenous sources of quinone stress in pathogenic bacteria, such as the fungal 6-brom-2-vinyl-chroman-4-on (55) or the plant-derived 1,4-naphthoquinone lapachol (32).…”

Section: Introductionmentioning

confidence: 99%

The MarR-Type Repressor MhqR Confers Quinone and Antimicrobial Resistance inStaphylococcus aureus

Fritsch

Loi

Busche

et al. 2019

Antioxidants & Redox Signaling

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Aims: Quinone compounds are electron carriers and have antimicrobial and toxic properties due to their mode of actions as electrophiles and oxidants. However, the regulatory mechanism of quinone resistance is less well understood in the pathogen Staphylococcus aureus. Results: Methylhydroquinone (MHQ) caused a thiol-specific oxidative and electrophile stress response in the S. aureus transcriptome as revealed by the induction of the PerR, QsrR, CstR, CtsR, and HrcA regulons. The SACOL2531-29 operon was most strongly upregulated by MHQ and was renamed as mhqRED operon based on its homology to the Bacillus subtilis locus. Here, we characterized the MarR-type regulator MhqR (SACOL2531) as quinone-sensing repressor of the mhqRED operon, which confers quinone and antimicrobial resistance in S. aureus. The mhqRED operon responds specifically to MHQ and less pronounced to pyocyanin and ciprofloxacin, but not to reactive oxygen species (ROS), hypochlorous acid, or aldehydes. The MhqR repressor binds specifically to a 9-9 bp inverted repeat (MhqR operator) upstream of the mhqRED operon and is inactivated by MHQ in vitro, which does not involve a thiol-based mechanism. In phenotypic assays, the mhqR deletion mutant was resistant to MHQ and quinone-like antimicrobial compounds, including pyocyanin, ciprofloxacin, norfloxacin, and rifampicin. In addition, the mhqR mutant was sensitive to sublethal ROS and 24 h post-macrophage infections but acquired an improved survival under lethal ROS stress and after long-term infections. Innovation: Our results provide a link between quinone and antimicrobial resistance via the MhqR regulon of S. aureus. Conclusion: The MhqR regulon was identified as a novel resistance mechanism towards quinone-like antimicrobials and contributes to virulence of S. aureus under long-term infections.

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Section: Introductionmentioning

confidence: 99%

The MarR-Type Repressor MhqR Confers Quinone and Antimicrobial Resistance inStaphylococcus aureus

Fritsch

Loi

Busche

et al. 2019

Antioxidants & Redox Signaling

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“…Oxidation of phenols results in an increase of hydroxylic groups and formation of quinones. These are known to react with sulfhydryl-groups and to give more or less stable compounds with proteins (HOFFMANN-OSTENHOF 1963). The reactivity of SH-and -S-S-groups depends on their steric situation, on the neighbourhood of other groups and on the extent of nucleophily of the R-Sions (ToRTSCHiNSKi 1963).…”

Section: Discussionmentioning

confidence: 99%

On the Toxicity of Oxidized Polyphenols

Lyr¹

1965

J Phytopathol

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“…The quinone moiety is involved in a wide variety of biochemical processes including electron transport and oxidative phosphorylation. Biological activities that have been reported for quinones and quinone derivatives include enzyme inhibition and antibacterial, antifungal, and anticancer activities. , Numerous structurally diverse quinone derivatives have been synthesized and investigated; one class of such compounds is the heterocyclic quinones, including imidazole derivatives of 1,4-naphthoquinones. , Naphth[2,3- d ]imidazole-4,9-dione and its 1-β- d -ribofuranosyl derivative were prepared in a study of naphthoquinone heterocycles and were found to be effective inhibitors of hypoxanthine phosphoribosyltransferase, which is involved in an initial step in purine nucleotide biosynthesis. In addition, the naphthoquinone psychorubrin was isolated as a cytotoxic natural product from Psychotria rubra ( Chiou Chie Mu ) (Rubiaceae) by this laboratory.…”

Section: Introductionmentioning

confidence: 99%

“…The quinone moiety is involved in a wide variety of biochemical processes 1 including electron transport and oxidative phosphorylation. Biological activities that have been reported for quinones and quinone derivatives include enzyme inhibition 2 and antibacterial, 3 antifungal, 4 and anticancer activities. 5,6 Numerous structurally diverse quinone derivatives have been synthesized and investigated; one class of such compounds is the heterocyclic quinones, including imidazole derivatives of 1,4-naphthoquinones.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Cytotoxicity of 1,2-Disubstituted Naphth[2,3-d]imidazole-4,9-diones and Related Compounds

et al. 1996

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As part of our continuing search for potential anticancer drug candidates that are selective against slowly growing solid tumors, we have synthesized several series of 1- and 2-substituted derivatives of the lead structure, 1-ethyl-2-methylnaphth[2,3-d]imidazole-4,9-dione (5). Their cytotoxic activity in the National Cancer Institute's in vitro cancer cell line panel is reported. In general, substitution of various alkyl, phenyl, or benzyl moieties did not improve activity, and compound 5 remains the most active naphth[2,3-d]imidazole-4,9-dione derivative. However, high levels of activity and selectivity were found with several related 2-(acylamino)-3-chloro-1,4-naphthoquinones (2f-j). Compound 2i, 2-[(2-fluorophenyl)acetamido]-3-chloro-1,4-naphthoquinone, has been selected for further in vivo testing and as an additional lead compound for further structural modification.

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Enzyme Inhibition by Quinones

Cited by 22 publications

References 48 publications

The MarR-Type Repressor MhqR Confers Quinone and Antimicrobial Resistance inStaphylococcus aureus

The MarR-Type Repressor MhqR Confers Quinone and Antimicrobial Resistance inStaphylococcus aureus

On the Toxicity of Oxidized Polyphenols

Synthesis and Cytotoxicity of 1,2-Disubstituted Naphth[2,3-d]imidazole-4,9-diones and Related Compounds

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