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British Journal of Pharmacology Jul 2017Azoreductases are flavoenzymes that have been characterized in a range of prokaryotes and eukaryotes. Bacterial azoreductases are associated with the activation of two... (Review)
Review
UNLABELLED
Azoreductases are flavoenzymes that have been characterized in a range of prokaryotes and eukaryotes. Bacterial azoreductases are associated with the activation of two classes of drug, azo drugs for the treatment of inflammatory bowel disease and nitrofuran antibiotics. The mechanism of reduction of azo compounds is presented; it requires tautomerisation of the azo compound to a quinoneimine and provides a unifying mechanism for the reduction of azo and quinone substrates by azoreductases. The importance of further work in the characterization of azoreductases from enteric bacteria is highlighted to aid in the development of novel drugs for the treatment of colon related disorders. Human azoreductases are known to play a crucial role in the metabolism of a number of quinone-containing cancer chemotherapeutic drugs. The mechanism of hydride transfer to quinones, which is shared not only between eukaryotic and prokaryotic azoreductases but also the wider family of NAD(P)H quinone oxidoreductases, is outlined. The importance of common single nucleotide polymorphisms (SNPs) in human azoreductases is described not only in cancer prognosis but also with regard to their effects on the efficacy of quinone drug-based cancer chemotherapeutic regimens. This highlights the need to screen patients for azoreductase SNPs ahead of treatment with these regimens.
LINKED ARTICLES
This article is part of a themed section on Drug Metabolism and Antibiotic Resistance in Micro-organisms. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.14/issuetoc.
Topics: Anti-Bacterial Agents; Antineoplastic Agents; Azo Compounds; Bacteria; Humans; NADH, NADPH Oxidoreductases; Neoplasms; Nitrofurans; Nitroreductases; Quinones
PubMed: 27487252
DOI: 10.1111/bph.13571 -
Molecules (Basel, Switzerland) Sep 2022Azo molecules, characterized by the presence of a -N=N- double bond, are widely used in various fields due to their sensitivity to external stimuli, ch as light. The... (Review)
Review
Azo molecules, characterized by the presence of a -N=N- double bond, are widely used in various fields due to their sensitivity to external stimuli, ch as light. The emergence of bacterial resistance has pushed research towards designing new antimicrobial molecules that are more efficient than those currently in use. Many authors have attempted to exploit the antimicrobial activity of azobenzene and to utilize their photoisomerization for selective control of the bioactivities of antimicrobial molecules, which is necessary for antibacterial therapy. This review will provide a systematic and consequential approach to coupling azobenzene moiety with active antimicrobial molecules and drugs, including small and large organic molecules, such as peptides. A selection of significant cutting-edge articles collected in recent years has been discussed, based on the structural pattern and antimicrobial performance, focusing especially on the photoactivity of azobenzene and the design of smart materials as the most targeted and desirable application.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Azo Compounds
PubMed: 36080413
DOI: 10.3390/molecules27175643 -
International Journal of Environmental... Apr 2022Azo dyes have become a staple in various industries, as colors play an important role in consumer choices. However, these dyes pose various health and environmental... (Review)
Review
Azo dyes have become a staple in various industries, as colors play an important role in consumer choices. However, these dyes pose various health and environmental risks. Although different wastewater treatments are available, the search for more eco-friendly options persists. Bioremediation utilizing microorganisms has been of great interest to researchers and industries, as the transition toward greener solutions has become more in demand through the years. This review tackles the health and environmental repercussions of azo dyes and its metabolites, available biological approaches to eliminate such dyes from the environment with a focus on the use of different microorganisms, enzymes that are involved in the degradation of azo dyes, and recent trends that could be applied for the treatment of azo dyes.
Topics: Azo Compounds; Biodegradation, Environmental; Coloring Agents
PubMed: 35457607
DOI: 10.3390/ijerph19084740 -
Food and Chemical Toxicology : An... Jun 1988
Topics: Attention Deficit Disorder with Hyperactivity; Azo Compounds; Child; Food Additives; Humans; Tartrazine
PubMed: 3169655
DOI: 10.1016/0278-6915(88)90014-2 -
Food and Chemical Toxicology : An... Aug 2023Azo dyes, including Tartrazine, Sunset Yellow, and Carmoisine, are added to foods to provide color, but they have no value with regard to nutrition, food preservation,... (Review)
Review
Azo dyes, including Tartrazine, Sunset Yellow, and Carmoisine, are added to foods to provide color, but they have no value with regard to nutrition, food preservation, or health benefits. Because of their availability, affordability, stability, and low cost, and because they provide intense coloration to the product without contributing unwanted flavors, the food industry often prefers to use synthetic azo dyes rather than natural colorants. Food dyes have been tested by regulatory agencies responsible for guaranteeing consumer safety. Nevertheless, the safety of these colorants remains controversial; they have been associated with adverse effects, particularly due to the reduction and cleavage of the azo bond. Here, we review the features, classification, regulation, toxicity, and alternatives to the use of azo dyes in food.
Topics: Azo Compounds; Tartrazine; Coloring Agents; Food; Food Industry; Food Coloring Agents
PubMed: 37429408
DOI: 10.1016/j.fct.2023.113935 -
Proceedings of the National Academy of... Dec 2002The ability to photoregulate enzyme activities could provide important new opportunities for development of diagnostic assays, sequential bioprocessing, and lab assays...
The ability to photoregulate enzyme activities could provide important new opportunities for development of diagnostic assays, sequential bioprocessing, and lab assays in both traditional and microfluidic formats. We show here that the photoinduced changes in the size and hydration of a "smart" polymer chain coil can be used to regulate substrate access and enzyme activity when conjugated to the enzyme at a specific point just outside the active site. The photoresponsive polymers thus serve jointly as antennae and actuators that reversibly respond to distinct optical signals to switch the polymer-enzyme conjugates on and off, and work when the conjugate is free in solution or when immobilized on magnetic beads.
Topics: Acrylamides; Acrylates; Azo Compounds; Cellulase; Kinetics; Light; Models, Molecular; Polymers; Ultraviolet Rays
PubMed: 12486222
DOI: 10.1073/pnas.262427799 -
Organic Letters Jun 2021Azoheteroarenes make up an emerging class of photoswitchable compounds with unique photophysical properties and advantages over traditional azobenzenes. Therefore,...
Azoheteroarenes make up an emerging class of photoswitchable compounds with unique photophysical properties and advantages over traditional azobenzenes. Therefore, methods for synthesizing azoheteroarenes are highly desirable. Here, we utilize azide-alkyne click chemistry to access arylazo-1,2,3-triazoles, a previously unexplored class of azoheteroarenes that exhibit high thermal stabilities and near-quantitative bidirectional photoconversion. Controlling the catalyst or 1,3-dipole grants access to both regioisomeric arylazotriazoles and arylazoisoxazoles, highlighting the versatility of our approach.
Topics: Alkynes; Azides; Azo Compounds; Catalysis; Click Chemistry; Molecular Structure; Triazoles
PubMed: 34019429
DOI: 10.1021/acs.orglett.1c01230 -
Journal of the American Chemical Society May 2022We present the synthesis, photophysical properties, and biological application of nontoxic 3-azo-conjugated BODIPY dyes as masked fluorescent biosensors of hypoxia-like...
We present the synthesis, photophysical properties, and biological application of nontoxic 3-azo-conjugated BODIPY dyes as masked fluorescent biosensors of hypoxia-like conditions. The synthetic methodology is based on an operationally simple N═N bond-forming protocol, followed by a Suzuki coupling, that allows for a direct access to simple and underexplored 3-azo-substituted BODIPY. These dyes can turn on their emission properties under both chemical and biological reductive conditions, including bacterial and human azoreductases, which trigger the azo bond cleavage, leading to fluorescent 3-amino-BODIPY. We have also developed a practical enzymatic protocol, using an immobilized bacterial azoreductase that allows for the evaluation of these azo-based probes and can be used as a model for the less accessible and expensive human reductase NQO1. Quantum mechanical calculations uncover the restructuration of the topography of the S potential energy surface following the reduction of the azo moiety and rationalize the fluorescent quenching event through the mapping of an unprecedented pathway. Fluorescent microscopy experiments show that these azos can be used to visualize hypoxia-like conditions within living cells.
Topics: Azo Compounds; Biosensing Techniques; Coloring Agents; Fluorescent Dyes; Humans; Hypoxia; Microscopy, Fluorescence
PubMed: 35486830
DOI: 10.1021/jacs.2c01197 -
Mutation Research. Genetic Toxicology... Aug 2019The mutagenicity of Direct Black 38, Sudan I, and Para Red were evaluated in the in vivo MutaMouse assay and the in vitro MutaMouse primary hepatocyte (PH) assay. Direct...
The mutagenicity of Direct Black 38, Sudan I, and Para Red were evaluated in the in vivo MutaMouse assay and the in vitro MutaMouse primary hepatocyte (PH) assay. Direct Black 38 is an International Agency for Research on Cancer (IARC) Group 1 carcinogen and a prototypical benzidine-based azo compound that requires azo-reduction to yield a DNA-reactive metabolite. Sudan I and Para Red are structurally related azo compounds that have been detected as illegal contaminants in foods. Sudan I is an in vivo mutagen, and both it and Para Red are known to be mutagenic in vitro. Sudan I is oxidized by hepatic and/or bladder enzymes to yield a mutagenic metabolite, but little is known about Para Red. In the present study, Direct Black 38 elicited a significant mutagenic response in the bone marrow, glandular stomach, small intestine and colon in vivo, and in PHs in vitro. Sudan I elicited a weak positive response in the bone marrow and a marginally significant treatment effect in the bladder (p = 0.059); it did not elicit a significant response in PHs in vitro. Para Red elicited a positive response in the colon, as well as in PHs in vitro, albeit at a cytotoxic concentration. The findings are well aligned with the known mechanisms of action of Direct Black 38 and Sudan I; they suggest that intestinal azo-reduction plays an important role in the activation of Para Red. The MutaMouse pH results illustrate the ability of this assay to detect chemicals requiring azo-reduction; however, they also demonstrate a gap in applicability domain, as MutaMouse PHs elicit a negative response following exposure to Sudan I. Elucidation of the mechanisms underlying this gap will require further study.
Topics: Animals; Azo Compounds; Cells, Cultured; Hepatocytes; Mice; Mutagenicity Tests; Mutagens; Naphthols; Organ Specificity; Primary Cell Culture; Structure-Activity Relationship
PubMed: 31326032
DOI: 10.1016/j.mrgentox.2019.06.003 -
Chemistry (Weinheim An Der Bergstrasse,... Feb 2021Light regulation of drug molecules has gained growing interest in biochemical and pharmacological research in recent years. In addition, a serious need for novel...
Light regulation of drug molecules has gained growing interest in biochemical and pharmacological research in recent years. In addition, a serious need for novel molecular targets of antibiotics has emerged presently. Herein, the development of a photocontrollable, azobenzene-based antibiotic precursor towards tryptophan synthase (TS), an essential metabolic multienzyme complex in bacteria, is presented. The compound exhibited moderately strong inhibition of TS in its E configuration and five times lower inhibition strength in its Z configuration. A combination of biochemical, crystallographic, and computational analyses was used to characterize the inhibition mode of this compound. Remarkably, binding of the inhibitor to a hitherto-unconsidered cavity results in an unproductive conformation of TS leading to noncompetitive inhibition of tryptophan production. In conclusion, we created a promising lead compound for combatting bacterial diseases, which targets an essential metabolic enzyme, and whose inhibition strength can be controlled with light.
Topics: Azo Compounds; Enzyme Inhibitors; Tryptophan Synthase
PubMed: 33078454
DOI: 10.1002/chem.202004061