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Food Chemistry Oct 2022The Amadori compound of glucose and l-alanyl-l-glutamine (Ala-Gln-ARP) was prepared and characterized by UPLC-MS/MS and NMR. There were no pyrazines produced by heated...
Structural diversity and concentration dependence of pyrazine formation: Exogenous amino substrates and reaction parameters during thermal processing of l-alanyl-l-glutamine Amadori compound.
The Amadori compound of glucose and l-alanyl-l-glutamine (Ala-Gln-ARP) was prepared and characterized by UPLC-MS/MS and NMR. There were no pyrazines produced by heated Ala-Gln-ARP alone due to the asynchronicity of regenerated l-alanyl-l-glutamine and α-dicarbonyl compounds. High temperature (130 °C) and long reaction time could facilitate the 2,5-dimethylpyrazine formation at a small concentration (33.4 ± 3.47 μg/L). The exogenous amino substrates would lower the formation temperature of pyrazines and make it to be generated effectively. Extra supplied l-alanyl-l-glutamine could generate 2,5-dimethylpyrazine at 110 °C, while higher temperature of 140 °C could strengthen the formation of 2,5-dimethylpyrazine (793 ± 119 μg/L) and stimulate the generation of other pyrazines, including methylpyrazine and 2,6-dimethylpyrazine. The exogenous alanine, glutamic acid, and glutamine was also beneficial to enhance the pyrazines formation, especially the glutamic acid. Furthermore, alkaline pH of thermal reaction made pyrazines increase significantly than in neutral medium and further enriched their species such as unsubstituted pyrazine and trimethylpyrazine.
Topics: Chromatography, Liquid; Dipeptides; Glutamic Acid; Glutamine; Maillard Reaction; Pyrazines; Tandem Mass Spectrometry
PubMed: 35594769
DOI: 10.1016/j.foodchem.2022.133144 -
ELife Sep 2023Drug resistance is a challenge in anticancer therapy. In many cases, cancers can be resistant to the drug prior to exposure, that is, possess intrinsic drug resistance....
Drug resistance is a challenge in anticancer therapy. In many cases, cancers can be resistant to the drug prior to exposure, that is, possess intrinsic drug resistance. However, we lack target-independent methods to anticipate resistance in cancer cell lines or characterize intrinsic drug resistance without a priori knowledge of its cause. We hypothesized that cell morphology could provide an unbiased readout of drug resistance. To test this hypothesis, we used HCT116 cells, a mismatch repair-deficient cancer cell line, to isolate clones that were resistant or sensitive to bortezomib, a well-characterized proteasome inhibitor and anticancer drug to which many cancer cells possess intrinsic resistance. We then expanded these clones and measured high-dimensional single-cell morphology profiles using Cell Painting, a high-content microscopy assay. Our imaging- and computation-based profiling pipeline identified morphological features that differed between resistant and sensitive cells. We used these features to generate a morphological signature of bortezomib resistance. We then employed this morphological signature to analyze a set of HCT116 clones (five resistant and five sensitive) that had not been included in the signature training dataset, and correctly predicted sensitivity to bortezomib in seven cases, in the absence of drug treatment. This signature predicted bortezomib resistance better than resistance to other drugs targeting the ubiquitin-proteasome system, indicating specificity for mechanisms of resistance to bortezomib. Our results establish a proof-of-concept framework for the unbiased analysis of drug resistance using high-content microscopy of cancer cells, in the absence of drug treatment.
Topics: Bortezomib; Microscopy; Boronic Acids; Pyrazines; Drug Resistance, Neoplasm; Cell Line, Tumor; Antineoplastic Agents; Proteasome Inhibitors; Proteasome Endopeptidase Complex; Apoptosis
PubMed: 37753907
DOI: 10.7554/eLife.91362 -
Mini Reviews in Medicinal Chemistry 2022Among antiviral drugs, the vast majority targets only one or two related viruses. The conventional model, one virus - one drug, significantly limits therapeutic options....
Among antiviral drugs, the vast majority targets only one or two related viruses. The conventional model, one virus - one drug, significantly limits therapeutic options. Therefore, in the strategy of controlling viral infections, there is a necessity to develop compounds with pleiotropic effects. Favipiravir (FPV) emerged as a strong candidate to become such a drug. The aim of the study is to present up-to-date information on the role of favipiravir in the treatment of viral respiratory infections. The anti-influenza activity of favipiravir has been confirmed in cell culture experiments, animal models, and clinical trials. Thoroughly different - from the previously registered drugs - mechanism of action suggests that FVP can be used as a countermeasure for the novel or re-emerging influenza virus infections. In recent months, favipiravir has been broadly investigated due to its potential efficacy in the treatment of COVID-19. Based on preclinical and clinical studies and a recently published meta-analysis it seems that favipiravir may be a promising antiviral drug in the treatment of patients with COVID-19. FPV is also effective against other RNA respiratory viruses and may be a candidate for the treatment of serious infections caused by human rhinovirus, respiratory syncytial virus, metapneumovirus, parainfluenza viruses and hantavirus pulmonary syndrome.
Topics: Amides; Animals; Antiviral Agents; COVID-19; Humans; Pyrazines; RNA Viruses; Virus Diseases; Viruses
PubMed: 35184710
DOI: 10.2174/1389557522666220218122744 -
Blood Advances Nov 2022
Topics: Benzaldehydes; Pyrazines; Pyrazoles
PubMed: 35984638
DOI: 10.1182/bloodadvances.2022007702 -
Molecules (Basel, Switzerland) Mar 2020According to the World Health Organization, tuberculosis is still in the top ten causes of death from a single infectious agent, killing more than 1.7 million people...
According to the World Health Organization, tuberculosis is still in the top ten causes of death from a single infectious agent, killing more than 1.7 million people worldwide each year. The rising resistance developed by against currently used antituberculars is an imperative to develop new compounds with potential antimycobacterial activity. As a part of our continuous research on structural derivatives of the first-line antitubercular pyrazinamide, we have designed, prepared, and assessed the in vitro whole cell growth inhibition activity of forty-two novel 5-alkylamino--phenylpyrazine-2-carboxamides with various length of the alkylamino chain (propylamino to octylamino) and various simple substituents on the benzene ring. Final compounds were tested against H37Ra and four other mycobacterial strains (, , , ) in a modified Microplate Alamar Blue Assay. We identified several candidate molecules with micromolar MIC against H37Ra and low in vitro cytotoxicity in HepG2 cell line, for example, -(4-hydroxyphenyl)-5-(pentylamino)pyrazine-2-carboxamide (, MIC = 3.91 µg/mL or 13.02 µM, SI > 38) and 5-(heptylamino)--(-tolyl)pyrazine-2-carboxamide (, MIC = 0.78 µg/mL or 2.39 µM, SI > 20). In a complementary screening, we evaluated the in vitro activity against bacterial and fungal strains of clinical importance. We observed no antibacterial activity and sporadic antifungal activity against the genus.
Topics: Antitubercular Agents; Drug Design; Drug Development; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Pyrazinamide; Pyrazines; Structure-Activity Relationship
PubMed: 32231166
DOI: 10.3390/molecules25071561 -
Current Medicinal Chemistry 2024Nowadays, antimicrobial therapies have become a very challenging issue because of a large diversity of reasons such as antimicrobial resistance, over consumption and... (Review)
Review
Nowadays, antimicrobial therapies have become a very challenging issue because of a large diversity of reasons such as antimicrobial resistance, over consumption and misuse of antimicrobial agents, . A modern, actual and very useful approach in antimicrobial therapy is represented by the use of hybrid drugs, especially combined five and six-membered ring azaheterocycles. In this review, we present an overview of the recent advanced data from the last five years in the field of hybrid diazine compounds with antimicrobial activity. In this respect, we highlight here essential data concerning the synthesis and antimicrobial activity of the main classes of diazine hybrids: pyridazine, pyrimidine, pyrazine, and their fused derivatives.
Topics: Humans; Pyrimidines; Anti-Infective Agents; Microbial Sensitivity Tests; Anti-Bacterial Agents; Pyrazines; Pyridazines; Bacteria
PubMed: 37073649
DOI: 10.2174/0929867330666230418104409 -
FASEB Journal : Official Publication of... Jun 2021Molecular recognition is a fundamental principle in biological systems. The olfactory detection of both food and predators via ecological relevant odorant cues are...
Molecular recognition is a fundamental principle in biological systems. The olfactory detection of both food and predators via ecological relevant odorant cues are abilities of eminent evolutionary significance for many species. Pyrazines are such volatile cues, some of which act as both human-centered key food odorants (KFOs) and semiochemicals. A pyrazine-selective odorant receptor has been elusive. Here we screened 2,3,5-trimethylpyrazine, a KFO and semiochemical, and 2,5-dihydro-2,4,5-trimethylthiazoline, an innate fear-associated non-KFO, against 616 human odorant receptor variants, in a cell-based luminescence assay. OR5K1 emerged as sole responding receptor. Tested against a comprehensive collection of 178 KFOs, we newly identified 18 pyrazines and (2R/2S)-4-methoxy-2,5-dimethylfuran-3(2H)-one as agonists. Notably, OR5K1 orthologs in mouse and domesticated species displayed a human-like, potency-ranked activation pattern of pyrazines, suggesting a domestication-led co-evolution of OR5K1 and its orthologs. In summary, OR5K1 is a specialized olfactory receptor across mammals for the detection of pyrazine-based key food odors and semiochemicals.
Topics: Animals; Evolution, Molecular; Food Analysis; Humans; Mice; Odorants; Pheromones; Phylogeny; Pyrazines; Receptors, Odorant; Smell
PubMed: 34047404
DOI: 10.1096/fj.202100224R -
Photochemical & Photobiological... Mar 2020The capability of three quaternized styryl-azinium iodides to bind cellular RNA has been tested by means of Fluorescence Confocal Microscopy imaging of stained MCF-7...
The capability of three quaternized styryl-azinium iodides to bind cellular RNA has been tested by means of Fluorescence Confocal Microscopy imaging of stained MCF-7 cells treated with RNase. Their association constants have been estimated through spectrophotometric and fluorimetric titrations with tRNA and compared to their affinity toward DNA. Transient absorption spectroscopy with femtosecond resolution confirmed the binding of the investigated compounds with tRNA and shed new light on the excited state dynamics of their complexes, by revealing a significant lengthening of the lifetime of S upon complexation, which parallels the fluorescence quantum yield enhancement.
Topics: Fluorescent Dyes; Humans; MCF-7 Cells; Microscopy, Confocal; Molecular Structure; Optical Imaging; Photochemical Processes; Pyrazines; RNA; Ribonucleases; Styrenes; Tumor Cells, Cultured
PubMed: 32147676
DOI: 10.1039/c9pp00465c -
Molecules (Basel, Switzerland) Jul 2021Ladybug taint (also known as ladybird taint) is a relatively recently recognized fault that has been identified in wines from a wide range of terroirs.... (Review)
Review
Ladybug taint (also known as ladybird taint) is a relatively recently recognized fault that has been identified in wines from a wide range of terroirs. Alkyl-methoxypyrazines-particularly 2-isopropyl-3-methoxypyrazine-have been determined as the causal compounds, and these are introduced into grape must during processing, when specific species of vineyard-dwelling Coccinellidae are incorporated into the harvested fruit. , and especially the invasive , are the beetles implicated, and climate change is facilitating wider dispersal and survivability of in viticultural regions worldwide. Affected wines are typically characterized as possessing excessively green, bell pepper-, and peanut-like aroma and flavor. In this paper, we review a range of vineyard practices that seek to reduce Coccinellidae densities, as well as both "standard" and novel wine treatments aimed at reducing alkyl-methoxypyrazine load. We conclude that while prevention of ladybug taint is preferable, there are several winery interventions that can remediate the quality of wine affected by this taint, although they vary in their relative efficacy and specificity.
Topics: Animals; Coleoptera; Food Contamination; Fruit; Odorants; Pyrazines; Vitis; Wine
PubMed: 34299616
DOI: 10.3390/molecules26144341 -
Physical Chemistry Chemical Physics :... Oct 2021Electron attachment and its equivalent in complex environments, single-electron reduction, are important in many biological processes. Here, we experimentally study the...
Electron attachment and its equivalent in complex environments, single-electron reduction, are important in many biological processes. Here, we experimentally study the electron attachment to favipiravir, a well-known antiviral agent. Electron attachment spectroscopy is used to explore the energetics of associative (AEA) and dissociative (DEA) electron attachment to isolated favipiravir. AEA dominates the interaction and the yields of the fragment anions after DEA are an order of magnitude lower than that of the parent anion. DEA primary proceeds decomposition of the CONH functional group, which is supported by reaction threshold calculations using methods. Mass spectrometry of small favipiravir-water clusters demonstrates that a lot of energy is transferred to the solvent upon electron attachment. The energy gained upon electron attachment, and the high stability of the parent anion were previously suggested as important properties for the action of several electron-affinic radiosensitizers. If any of these mechanisms cause synergism in chemo-radiation therapy, favipiravir could be repurposed as a radiosensitizer.
Topics: Amides; Electrons; Pyrazines; Water
PubMed: 34382983
DOI: 10.1039/d1cp02686k