-
Biomolecules Feb 2021Nitroaromatic antibiotics show activity against anaerobic bacteria and parasites, finding use in the treatment of infections, tuberculosis, trichomoniasis, human... (Review)
Review
Nitroaromatic antibiotics show activity against anaerobic bacteria and parasites, finding use in the treatment of infections, tuberculosis, trichomoniasis, human African trypanosomiasis, Chagas disease and leishmaniasis. Despite this activity and a clear need for the development of new treatments for these conditions, the associated toxicity and lack of clear mechanisms of action have limited their therapeutic development. Nitroaromatic antibiotics require reductive bioactivation for activity and this reductive metabolism can convert the nitro group to nitric oxide (NO) or a related reactive nitrogen species (RNS). As nitric oxide plays important roles in the defensive immune response to bacterial infection through both signaling and redox-mediated pathways, defining controlled NO generation pathways from these antibiotics would allow the design of new therapeutics. This review focuses on the release of nitrogen oxide species from various nitroaromatic antibiotics to portend the increased ability for these compounds to positively impact infectious disease treatment.
Topics: Activation, Metabolic; Anti-Bacterial Agents; Nitric Oxide Donors; Nitrogen Oxides; Oxidation-Reduction; Reactive Nitrogen Species
PubMed: 33673069
DOI: 10.3390/biom11020267 -
International Journal of Molecular... Sep 2022Nitric oxide (NO) is an active and critical nitrogen oxide in the microbe-driven nitrogen biogeochemical cycle, and is of great interest to medicine and the biological... (Review)
Review
Nitric oxide (NO) is an active and critical nitrogen oxide in the microbe-driven nitrogen biogeochemical cycle, and is of great interest to medicine and the biological sciences. As a gas molecule prior to oxygen, NO respiration represents an early form of energy generation via various reactions in prokaryotes. Major enzymes for endogenous NO formation known to date include two types of nitrite reductases in denitrification, hydroxylamine oxidoreductase in ammonia oxidation, and NO synthases (NOSs). While the former two play critical roles in shaping electron transport pathways in bacteria, NOSs are intracellular enzymes catalyzing metabolism of certain amino acids and have been extensively studied in mammals. NO interacts with numerous cellular targets, most of which are redox-active proteins. Doing so, NO plays harmful and beneficial roles by affecting diverse biological processes within bacterial physiology. Here, we discuss recent advances in the field, including NO-forming enzymes, the molecular mechanisms by which these enzymes function, physiological roles of bacterial NOSs, and regulation of NO homeostasis in bacteria.
Topics: Amino Acids; Ammonia; Animals; Bacteria; Mammals; Nitric Oxide; Nitrite Reductases; Nitrogen; Nitrogen Oxides; Oxygen
PubMed: 36142682
DOI: 10.3390/ijms231810778 -
Nitric Oxide : Biology and Chemistry Aug 2022The human microbiome comprises ∼10-10 microbial cells which form a symbiotic relationship with the host and play a critical role in the regulation of human metabolism.... (Review)
Review
The human microbiome comprises ∼10-10 microbial cells which form a symbiotic relationship with the host and play a critical role in the regulation of human metabolism. In the oral cavity, several species of bacteria are capable of reducing nitrate to nitrite; a key precursor of the signaling molecule nitric oxide. Nitric oxide has myriad physiological functions, which include the maintenance of cardiovascular homeostasis and the regulation of acute and chronic responses to exercise. This article provides a brief narrative review of the research that has explored how diversity and plasticity of the oral microbiome influences nitric oxide bioavailability and related physiological outcomes. There is unequivocal evidence that dysbiosis (e.g. through disease) or disruption (e.g. by use of antiseptic mouthwash or antibiotics) of the oral microbiota will suppress nitric oxide production via the nitrate-nitrite-nitric oxide pathway and negatively impact blood pressure. Conversely, there is preliminary evidence to suggest that proliferation of nitrate-reducing bacteria via the diet or targeted probiotics can augment nitric oxide production and improve markers of oral health. Despite this, it is yet to be established whether purposefully altering the oral microbiome can have a meaningful impact on exercise performance. Future research should determine whether alterations to the composition and metabolic activity of bacteria in the mouth influence the acute responses to exercise and the physiological adaptations to exercise training.
Topics: Bacteria; Exercise; Humans; Microbiota; Nitrates; Nitric Oxide; Nitrites; Nitrogen Oxides
PubMed: 35636654
DOI: 10.1016/j.niox.2022.05.004 -
Frontiers in Bioscience (Landmark... Jan 2019Mammalian NO-Synthases (NOSs) are the enzymatic sources of Nitric Oxide (NO°), a paradigmatic gasotransmitter involved in many (patho)-physiological processes. The... (Review)
Review
Mammalian NO-Synthases (NOSs) are the enzymatic sources of Nitric Oxide (NO°), a paradigmatic gasotransmitter involved in many (patho)-physiological processes. The increasing number of available genomes led to the identification of hundreds of new NOS proteins throughout the kingdoms of life, calling for a global investigation of this family of proteins. These new NOSs are commonly believed to share the same structure, functioning and role as mammalian NOSs. The scope of this article is to highlight the singularity of these NOSs and to describe their complex structural and functional diversity. NOS appears as a unique enzymatic machinery that exhibits a complex Structure - Activity - Function relationship. Its sophisticated redox mechanism and enzymatic regulation, coupled to the vast biological chemistry of reactive nitrogen species, leads to a specific cross-talk between NOS catalysis and its biological environment that implies a complex evolution of NOS function. This paper addresses the relationship between structure, function and evolution of NOS proteins using three NOS model families and advocates for an integrative and interdisciplinary approach that combines modelling studies, structural characterization, and functional investigations.
Topics: Animals; Archaeal Proteins; Bacterial Proteins; Biocatalysis; Humans; Nitric Oxide Synthase; Nitrogen Oxides; Phylogeny; Plant Proteins
PubMed: 30468649
DOI: 10.2741/4711 -
Journal of the American College of... Nov 2017The use of nitroglycerin in the treatment of angina pectoris began not long after its original synthesis in 1847. Since then, the discovery of nitric oxide as a... (Review)
Review
The use of nitroglycerin in the treatment of angina pectoris began not long after its original synthesis in 1847. Since then, the discovery of nitric oxide as a biological effector and better understanding of its roles in vasodilation, cell permeability, platelet function, inflammation, and other vascular processes have advanced our knowledge of the hemodynamic (mostly mediated through vasodilation of capacitance and conductance arteries) and nonhemodynamic effects of organic nitrate therapy, via both nitric oxide-dependent and -independent mechanisms. Nitrates are rapidly absorbed from mucous membranes, the gastrointestinal tract, and the skin; thus, nitroglycerin is available in a number of preparations for delivery via several routes: oral tablets, sublingual tablets, buccal tablets, sublingual spray, transdermal ointment, and transdermal patch, as well as intravenous formulations. Organic nitrates are commonly used in the treatment of cardiovascular disease, but clinical data limit their use mostly to the treatment of angina. They are also used in the treatment of subsets of patients with heart failure and pulmonary hypertension. One major limitation of the use of nitrates is the development of tolerance. Although several agents have been studied for use in the prevention of nitrate tolerance, none are currently recommended owing to a paucity of supportive clinical data. Only 1 method of preventing nitrate tolerance remains widely accepted: the use of a dosing strategy that provides an interval of no or low nitrate exposure during each 24-h period. Nitric oxide's important role in several cardiovascular disease mechanisms continues to drive research toward finding novel ways to affect both endogenous and exogenous sources of this key molecular mediator.
Topics: Animals; Cardiovascular Agents; Cardiovascular Diseases; Drug Administration Routes; Humans; Nitrogen Oxides; Nitroglycerin
PubMed: 29096811
DOI: 10.1016/j.jacc.2017.09.1064 -
ELife Jun 2019Beewolf wasp eggs release nitrogen oxides to provide protection against fungi and other microbes.
Beewolf wasp eggs release nitrogen oxides to provide protection against fungi and other microbes.
Topics: Animals; Bees; Nitrogen Oxides; Predatory Behavior; Wasps
PubMed: 31188127
DOI: 10.7554/eLife.48268 -
British Journal of Pharmacology Aug 2013Biological nitrogen oxide signalling and stress is an area of extreme clinical, pharmacological, toxicological, biochemical and chemical research interest. The utility... (Review)
Review
Biological nitrogen oxide signalling and stress is an area of extreme clinical, pharmacological, toxicological, biochemical and chemical research interest. The utility of nitric oxide and derived species as signalling agents is due to their novel and vast chemical interactions with a variety of biological targets. Herein, the chemistry associated with the interaction of the biologically relevant nitrogen oxide species with fundamental biochemical targets is discussed. Specifically, the chemical interactions of nitrogen oxides with nucleophiles (e.g. thiols), metals (e.g. hemeproteins) and paramagnetic species (e.g. dioxygen and superoxide) are addressed. Importantly, the terms associated with the mechanisms by which NO (and derived species) react with their respective biological targets have been defined by numerous past chemical studies. Thus, in order to assist researchers in referring to chemical processes associated with nitrogen oxide biology, the vernacular associated with these chemical interactions is addressed.
Topics: Animals; Hemeproteins; Metalloproteins; Metals; Nitric Oxide; Nitrosation; Reactive Nitrogen Species; S-Nitrosothiols; Signal Transduction
PubMed: 23617570
DOI: 10.1111/bph.12217 -
International Journal of Molecular... Nov 2017Nitroxides are stable free radicals that contain a nitroxyl group with an unpaired electron. In this paper, we present the properties and application of nitroxides as... (Review)
Review
Nitroxides are stable free radicals that contain a nitroxyl group with an unpaired electron. In this paper, we present the properties and application of nitroxides as antioxidants and anticancer drugs. The mostly used nitroxides in biology and medicine are a group of heterocyclic nitroxide derivatives of piperidine, pyrroline and pyrrolidine. The antioxidant action of nitroxides is associated with their redox cycle. Nitroxides, unlike other antioxidants, are characterized by a catalytic mechanism of action associated with a single electron oxidation and reduction reaction. In biological conditions, they mimic superoxide dismutase (SOD), modulate hemoprotein's catalase-like activity, scavenge reactive free radicals, inhibit the Fenton and Haber-Weiss reactions and suppress the oxidation of biological materials (peptides, proteins, lipids, etc.). The use of nitroxides as antioxidants against oxidative stress induced by anticancer drugs has also been investigated. The application of nitroxides and their derivatives as anticancer drugs is discussed in the contexts of breast, hepatic, lung, ovarian, lymphatic and thyroid cancers under in vivo and in vitro experiments. In this article, we focus on new natural spin-labelled derivatives such as camptothecin, rotenone, combretastatin, podophyllotoxin and others. The applications of nitroxides in the aging process, cardiovascular disease and pathological conditions were also discussed.
Topics: Aging; Animals; Antineoplastic Agents; Antioxidants; Disease Susceptibility; Doxorubicin; Humans; Neoplasms; Nitrogen Oxides; Oxidation-Reduction; Oxidative Stress; Superoxide Dismutase
PubMed: 29165366
DOI: 10.3390/ijms18112490 -
International Journal of Molecular... Dec 2022Cancer is a leading cause of death worldwide. Conventional methods of cancer treatment, including chemotherapy and radiotherapy, are associated with multiple side...
Cancer is a leading cause of death worldwide. Conventional methods of cancer treatment, including chemotherapy and radiotherapy, are associated with multiple side effects. Recently, photodynamic therapy (PDT) has emerged as an effective therapeutic modality for cancer treatment without adversely affecting normal tissue. In this study, we synthesized nitrogen doped graphene (NDG) and conjugated it with MnO nanoparticles to produce NDG-MnO nanocomposite with the aim of testing its bimodal performance including PDT and magnetic resonance imaging (MRI). We did not use any linker or binder for conjugation between NDG and MnO, rather they were anchored by a milling process. The results of cell viability analysis showed that NDG-MnO nanocomposites caused significant cell death under laser irradiation, while control and MnO nanoparticles showed negligible cell death. We observed increased generation of singlet oxygen after exposure of NDG-MnO nanocomposites, which was directly proportional to the duration of laser irradiation. The results of MRI showed concentration dependent enhancement of signal intensity with an increasing concentration of NDG-MnO nanocomposites. In conclusion, NDG-MnO nanocomposites did not cause any cytotoxicity under physiological conditions. However, they produced significant and dose-dependent cytotoxicity in cancer cells after laser irradiation. NDG-MnO nanocomposites also exhibited concentration-dependent MRI contrast property, suggesting their possible application for cancer imaging. Further studies are warranted to test the theranostic potential of NDG-MnO nanocomposites using animal models of cancer.
Topics: Animals; Cell Line, Tumor; Photochemotherapy; Nanocomposites; Magnetic Resonance Imaging; Nitrogen Oxides; Nitrogen
PubMed: 36499412
DOI: 10.3390/ijms232315087 -
Chemical Society Reviews Oct 2015The oxides of nitrogen (chiefly NO, NO3(-), NO2(-) and N2O) are key components of the natural nitrogen cycle and are intermediates in a range of processes of enormous... (Review)
Review
The oxides of nitrogen (chiefly NO, NO3(-), NO2(-) and N2O) are key components of the natural nitrogen cycle and are intermediates in a range of processes of enormous biological, environmental and industrial importance. Nature has evolved numerous enzymes which handle the conversion of these oxides to/from other small nitrogen-containing species and there also exist a number of heterogeneous catalysts that can mediate similar reactions. In the chemical space between these two extremes exist metal-ligand coordination complexes that are easier to interrogate than heterogeneous systems and simpler in structure than enzymes. In this Tutorial Review, we will examine catalysts for the inter-conversions of the various nitrogen oxides that are based on such complexes, looking in particular at more recent examples that take inspiration from the natural systems.
Topics: Coordination Complexes; Ligands; Molecular Structure; Nitrogen Cycle; Nitrogen Oxides; Oxidation-Reduction; Oxidoreductases
PubMed: 26158348
DOI: 10.1039/c5cs00269a