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Molecules (Basel, Switzerland) Aug 2020Chemistry of nitro groups and nitro compounds has long been intensively studied. Despite their long history, new reactions and methodologies are still being found today....
Chemistry of nitro groups and nitro compounds has long been intensively studied. Despite their long history, new reactions and methodologies are still being found today. This is due to the diverse reactivity of the nitro group. The importance of nitro chemistry will continue to increase in the future in terms of elaborate synthesis. In this article, we will take a walk through the recent advances in nitro chemistry that have been made in past decades.
Topics: Chemistry; Nitro Compounds
PubMed: 32806751
DOI: 10.3390/molecules25163680 -
Nitric Oxide : Biology and Chemistry Sep 2018Nitro-fatty acids (NO-FA) are pleiotropic modulators of redox signaling pathways. Their effects on inflammatory signaling have been studied in great detail in cell,... (Review)
Review
Nitro-fatty acids (NO-FA) are pleiotropic modulators of redox signaling pathways. Their effects on inflammatory signaling have been studied in great detail in cell, animal and clinical models primarily using exogenously administered nitro-oleic acid. While we know a considerable amount regarding NO-FA signaling, endogenous formation and metabolism is relatively unexplored. This review will cover what is currently known regarding the proposed mechanisms of NO-FA formation, dietary modulation of endogenous NO-FA levels, pathways of NO-FA metabolism and the detection of NO-FA and corresponding metabolites.
Topics: Animals; Fatty Acids; Humans; Nitric Oxide; Nitro Compounds; Oxidation-Reduction
PubMed: 30006146
DOI: 10.1016/j.niox.2018.07.003 -
Parasitology Apr 2022Cutaneous leishmaniasis (CL) is a spectrum of clinical manifestations characterized by severe skin ulcerations that leads to social stigma. There are limited treatment...
Cutaneous leishmaniasis (CL) is a spectrum of clinical manifestations characterized by severe skin ulcerations that leads to social stigma. There are limited treatment options for CL, and the available drugs are becoming less efficacious due to drug resistance. More efficacious and safer antileishmanial drugs are needed. In this study, the biological effect of seven synthetically accessible nitroaromatic compounds was evaluated in vitro against amastigotes of Leishmania amazonensis, followed by in vivo evaluation using mouse models of CL. Two compounds (6 and 7) were active against amastigotes in vitro [half-maximal effective concentration (EC50): 4.57 ± 0.08 and 9.19 ± 0.68 μm, respectively], with selectivity indexes >50, and the other compounds were not selective. In vivo, compounds 6 and 7 (10 mg kg−1, twice a day for 14 days) failed to reduce skin lesion sizes and parasite loads determined by light microscopy of lesion imprints and quantitative polymerase chain reaction. Nevertheless, the in vitro leishmanicidal efficacy sustained their use as templates for nitroimidazole-based antileishmanial drug discovery programmes focusing on analogues with more suitable properties.
Topics: Animals; Antiprotozoal Agents; Leishmania mexicana; Leishmaniasis, Cutaneous; Mice; Mice, Inbred BALB C; Nitro Compounds
PubMed: 35109958
DOI: 10.1017/S0031182021002079 -
Antimicrobial Agents and Chemotherapy Sep 2023Nitro-containing compounds have emerged as important agents in the control of tuberculosis (TB). From a whole-cell high-throughput screen for (Mtb) growth inhibitors,...
Nitro-containing compounds have emerged as important agents in the control of tuberculosis (TB). From a whole-cell high-throughput screen for (Mtb) growth inhibitors, 10 nitro-containing compounds were prioritized for characterization and mechanism of action studies. HC2209, HC2210, and HC2211 are nitrofuran-based prodrugs that need the cofactor F machinery for activation. Unlike pretomanid which depends only on deazaflavin-dependent nitroreductase (Ddn), these nitrofurans depend on Ddn and possibly another F-dependent reductase for activation. These nitrofurans also differ from pretomanid in their potent activity against . Four dinitrobenzamides (HC2217, HC2226, HC2238, and HC2239) and a nitrofuran (HC2250) are proposed to be inhibitors of decaprenyl-phosphoryl-ribose 2'-epimerase 1 (DprE1), based on isolation of resistant mutations in . Unlike other DprE1 inhibitors, HC2250 was found to be potent against non-replicating persistent bacteria, suggesting additional targets. Two of the compounds, HC2233 and HC2234, were found to have potent, sterilizing activity against replicating and non-replicating Mtb , but a proposed mechanism of action could not be defined. In a pilot efficacy study, HC2210 was orally bioavailable and efficacious in reducing bacterial load by ~1 log in a chronic murine TB infection model.
Topics: Animals; Mice; Nitro Compounds; Nitroimidazoles; Nitrofurans; Bacterial Load
PubMed: 37610224
DOI: 10.1128/aac.00474-23 -
International Journal of Molecular... Aug 2021Nitroaromatic compounds (ArNO) maintain their importance in relation to industrial processes, environmental pollution, and pharmaceutical application. The manifestation... (Review)
Review
Nitroaromatic compounds (ArNO) maintain their importance in relation to industrial processes, environmental pollution, and pharmaceutical application. The manifestation of toxicity/therapeutic action of nitroaromatics may involve their single- or two-electron reduction performed by various flavoenzymes and/or their physiological redox partners, metalloproteins. The pivotal and still incompletely resolved questions in this area are the identification and characterization of the specific enzymes that are involved in the bioreduction of ArNO and the establishment of their contribution to cytotoxic/therapeutic action of nitroaromatics. This review addresses the following topics: (i) the intrinsic redox properties of ArNO, in particular, the energetics of their single- and two-electron reduction in aqueous medium; (ii) the mechanisms and structure-activity relationships of reduction in ArNO by flavoenzymes of different groups, dehydrogenases-electrontransferases (NADPH:cytochrome P-450 reductase, ferredoxin:NADP(H) oxidoreductase and their analogs), mammalian NAD(P)H:quinone oxidoreductase, bacterial nitroreductases, and disulfide reductases of different origin (glutathione, trypanothione, and thioredoxin reductases, lipoamide dehydrogenase), and (iii) the relationships between the enzymatic reactivity of compounds and their activity in mammalian cells, bacteria, and parasites.
Topics: Animals; Bacteria; Bacterial Proteins; Cytotoxins; Electrons; Flavoproteins; Humans; Nitro Compounds; Oxidation-Reduction; Oxidoreductases
PubMed: 34445240
DOI: 10.3390/ijms22168534 -
Poultry Science Mar 2020Coccidiosis is a disease caused by Eimeria spp., resulting in approximately 3 billion US dollar loss in the poultry industry annually. The present study evaluated the...
Coccidiosis is a disease caused by Eimeria spp., resulting in approximately 3 billion US dollar loss in the poultry industry annually. The present study evaluated the effects of potential feed additives, 2-Nitro-1-propanol (NP) and nitroethanol (NE), on control of coccidiosis. An in vitro experiment indicated that both NP and NE inhibited the development of sporozoites in Madin-Darby bovine kidney cells (MDBK). The in vivo study was further conducted to evaluate the effects of NP and NE on growth performance, nitrogen-corrected apparent metabolizable energy (AMEn), and intestinal lesion scores of broilers challenged with Eimeria spps. Six treatments were tested in the study, including the nonchallenged control, challenged control, 100 ppm NP, 200 ppm NP, 100 ppm NE, and 200 ppm NE. Broilers were fed the treatment diets from day 12 until the end of the trial. All birds except the unchallenged control were challenged with Eimeria maxima, Eimeria tenella, and Eimeria acervulina on day 14. The growth performance was calculated, and the intestinal lesion was scored on day 20. The results showed that Eimeria challenge significantly reduced growth performance, increased intestinal lesion scores, and decreased AMEn compared with the nonchallenged control group. Birds fed with 200 ppm of NP had reduced growth performance compared with the nonchallenged control and challenged control. However, the supplementation of NP significantly improved AMEn and reduced cecal damage. Overall, NP and NE reduced sporozoites numbers in the MDBK cells. NP improved dietary digestibility of energy and reduces lesion scores in the ceca but could not maintain growth performance in broiler chickens infected with Eimeria spp.
Topics: Animal Feed; Animals; Chickens; Coccidiosis; Diet; Dietary Supplements; Dose-Response Relationship, Drug; Eimeria; Male; Nitro Compounds; Poultry Diseases; Propanols; Random Allocation
PubMed: 32111308
DOI: 10.1016/j.psj.2019.11.026 -
Investigational New Drugs Jun 2016The 'holy grail' in radiation oncology is to improve the outcome of radiation therapy (RT) with a radiosensitizer-a systemic chemical/biochemical agent that additively... (Review)
Review
The 'holy grail' in radiation oncology is to improve the outcome of radiation therapy (RT) with a radiosensitizer-a systemic chemical/biochemical agent that additively or synergistically sensitizes tumor cells to radiation in the absence of significant toxicity. Similar to the oxygen effect, in which DNA bases modified by reactive oxygen species prevent repair of the cellular radiation damage, these compounds in general magnify free radical formation, leading to the permanent "fixation" of the resultant chemical change in the DNA structure. The purpose of this review is to present the origin story of the radiosensitizer, RRx-001, which emerged from the aerospace industry. The activity of RRx-001 as a chemosensitizer in multiple tumor types and disease states including malaria, hemorrhagic shock and sickle cell anemia, are the subject of future reviews.
Topics: Animals; Antineoplastic Agents; Azetidines; Humans; Neoplasms; Nitro Compounds; Radiation-Sensitizing Agents; Reactive Oxygen Species
PubMed: 26841903
DOI: 10.1007/s10637-016-0326-y -
Trends in Endocrinology and Metabolism:... Aug 2019In addition to supporting cellular energetic demands and providing building blocks for lipid synthesis, fatty acids (FAs) are precursors of potent signaling molecules.... (Review)
Review
In addition to supporting cellular energetic demands and providing building blocks for lipid synthesis, fatty acids (FAs) are precursors of potent signaling molecules. In particular, the presence of conjugated double bonds on the fatty-acyl chain provides a preferential target for nitration generating nitro-FAs (NO-FAs). The formation of NO-FAs is a nonenzymatic process that requires reactive nitrogen species and occurs locally at the site of inflammation or during gastric acidification. NO-FAs are electrophilic and display pleiotropic signaling actions through reversible protein alkylation. This review focuses on the endogenously formed NO-FAs' mechanism of absorption, systemic distribution, signaling, and preclinical models. Understanding the dynamics of these processes will facilitate targeted dietary interventions and further the current pharmacological development aimed at low-grade inflammatory diseases.
Topics: Animals; Fatty Acids; Humans; Inflammation; Nitro Compounds; Nitrogen Dioxide; Signal Transduction
PubMed: 31196614
DOI: 10.1016/j.tem.2019.04.009 -
Redox Biology May 2019Nitro-fatty acids (NO-FA) undergo reversible Michael adduction reactions with cysteine and histidine residues leading to the post-translational modification (PTM) of... (Review)
Review
Nitro-fatty acids (NO-FA) undergo reversible Michael adduction reactions with cysteine and histidine residues leading to the post-translational modification (PTM) of proteins. This electrophilic character of NO-FA is strictly related to their biological roles. The NO-FA-induced PTM of signaling proteins can lead to modifications in protein structure, function, and subcellular localization. The nitro lipid-protein adducts trigger a series of downstream signaling events that culminates with anti-inflammatory, anti-hypertensive, and cytoprotective effects mediated by NO-FA. These lipoxidation adducts have been detected and characterized both in model systems and in biological samples by using mass spectrometry (MS)-based approaches. These MS approaches allow to unequivocally identify the adduct together with the targeted residue of modification. The identification of the modified proteins allows inferring on the possible impact of the NO-FA-induced modification. This review will focus on MS-based approaches as valuable tools to identify NO-FA-protein adducts and to unveil the biological effect of this lipoxidation adducts.
Topics: Biomarkers; Fatty Acids; Lipids; Lipoproteins; Mass Spectrometry; Molecular Structure; Nitrates; Nitro Compounds; Oxidation-Reduction; Protein Processing, Post-Translational; Signal Transduction
PubMed: 30718106
DOI: 10.1016/j.redox.2019.101106 -
Molecules (Basel, Switzerland) Jul 2020Nitrated-pyrazole-based energetic compounds have attracted wide publicity in the field of energetic materials (EMs) due to their high heat of formation, high density,... (Review)
Review
Nitrated-pyrazole-based energetic compounds have attracted wide publicity in the field of energetic materials (EMs) due to their high heat of formation, high density, tailored thermal stability, and detonation performance. Many nitrated-pyrazole-based energetic compounds have been developed to meet the increasing demands of high power, low sensitivity, and eco-friendly environment, and they have good applications in explosives, propellants, and pyrotechnics. Continuous and growing efforts have been committed to promote the rapid development of nitrated-pyrazole-based EMs in the last decade, especially through large amounts of Chinese research. Some of the ultimate aims of nitrated-pyrazole-based materials are to develop potential candidates of castable explosives, explore novel insensitive high energy materials, search for low cost synthesis strategies, high efficiency, and green environmental protection, and further widen the applications of EMs. This review article aims to present the recent processes in the synthesis and physical and explosive performances of the nitrated-pyrazole-based Ems, including monopyrazoles with nitro, bispyrazoles with nitro, nitropyrazolo[4,3-]pyrazoles, and their derivatives, and to comb the development trend of these compounds. This review intends to prompt fresh concepts for designing prominent high-performance nitropyrazole-based EMs.
Topics: Explosive Agents; Nitrates; Nitro Compounds; Pyrazoles; Thermodynamics
PubMed: 32751631
DOI: 10.3390/molecules25153475