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Blood Cancer Journal Nov 2023
Topics: Humans; Bortezomib; Multiple Myeloma; Standard of Care; Pyrazines; Physicians
PubMed: 37926718
DOI: 10.1038/s41408-023-00937-0 -
Talanta Jul 2023Gas chromatography coupled with ion mobility spectrometry (IMS) is an analytical tool which is rapidly becoming widespread in the analysis of food volatiles. Despite...
Gas chromatography coupled with ion mobility spectrometry (IMS) is an analytical tool which is rapidly becoming widespread in the analysis of food volatiles. Despite this increasing popularity, an assessment of the IMS response for several flavor compound classes is not yet available. This study focuses on alkyl pyrazines and their determination in roasted hazelnut pastes. These Maillard reaction products are crucial to determine the aromatic profile of roasted foods and are suitable markers for industrial roasting monitoring. The instrumental response of 8 alkyl pyrazines was studied using a model matrix and a matrix matching approach. The results showed a relevant effect of the pyrazine ring substitution pattern on the concentration-response curve trends, highlighting that an external standardization of the IMS response is required to make possible relative abundance comparisons between analytes. A response standardization was therefore developed and applied to determine alkyl pyrazines in samples with different roasting intensity and geographical and botanical origin.
Topics: Gas Chromatography-Mass Spectrometry; Corylus; Pyrazines; Ion Mobility Spectrometry; Volatile Organic Compounds
PubMed: 37088040
DOI: 10.1016/j.talanta.2023.124568 -
BioMed Research International 2016Tetramethylpyrazine (TMP), a pharmacologically active component isolated from the rhizome of the Chinese herb Rhizoma Chuanxiong (Chuanxiong), has been clinically used... (Review)
Review
Tetramethylpyrazine (TMP), a pharmacologically active component isolated from the rhizome of the Chinese herb Rhizoma Chuanxiong (Chuanxiong), has been clinically used in China and Southeast Asian countries for the prevention and treatment of cardiovascular diseases (CVDs) for about fifty years. The pharmacological effects of TMP on the cardiovascular system have attracted great interest. Emerging experimental studies and clinical trials have demonstrated that TMP prevents atherosclerosis as well as ischemia-reperfusion injury. The cardioprotective effects of TMP are mainly related to its antioxidant, anti-inflammatory, or calcium-homeostasis effects. This review focuses on the roles and mechanisms of action of TMP in the cardiovascular system and provides a novel perspective on TMP's clinical use.
Topics: Animals; Anti-Inflammatory Agents; Antioxidants; Atherosclerosis; Calcium; China; Humans; Pinellia; Pyrazines; Reperfusion Injury; Rhizome
PubMed: 27314011
DOI: 10.1155/2016/2430329 -
CPT: Pharmacometrics & Systems... May 2020In 2014, our research network was involved in the evaluation of favipiravir, an anti-influenza polymerase inhibitor, against Ebola virus. In this review, we discuss how... (Review)
Review
In 2014, our research network was involved in the evaluation of favipiravir, an anti-influenza polymerase inhibitor, against Ebola virus. In this review, we discuss how mathematical modeling was used, first to propose a relevant dosing regimen in humans, and then to optimize its antiviral efficacy in a nonhuman primate (NHP) model. The data collected in NHPs were finally used to develop a model of Ebola pathogenesis integrating the interactions among the virus, the innate and adaptive immune response, and the action of favipiravir. We conclude the review of this work by discussing how these results are of relevance for future human studies in the context of Ebola virus, but also for other emerging viral diseases for which no therapeutics are available.
Topics: Amides; Animals; Antiviral Agents; Clinical Trials as Topic; Disease Models, Animal; Dose-Response Relationship, Drug; Hemorrhagic Fever, Ebola; Humans; Models, Theoretical; Pyrazines
PubMed: 32198838
DOI: 10.1002/psp4.12510 -
Blood Advances Sep 2022Despite the clinical benefit associated with gilteritinib in relapsed/refractory acute myeloid leukemia (AML), most patients eventually develop resistance through...
Despite the clinical benefit associated with gilteritinib in relapsed/refractory acute myeloid leukemia (AML), most patients eventually develop resistance through unknown mechanisms. To delineate the mechanistic basis of resistance to gilteritinib, we performed targeted sequencing and scRNASeq on primary FLT3-ITD-mutated AML samples. Co-occurring mutations in RAS pathway genes were the most common genetic abnormalities, and unresponsiveness to gilteritinib was associated with increased expression of bone marrow-derived hematopoietic cytokines and chemokines. In particular, we found elevated expression of the TEK-family kinase, BMX, in gilteritinib-unresponsive patients pre- and post-treatment. BMX contributed to gilteritinib resistance in FLT3-mutant cell lines in a hypoxia-dependent manner by promoting pSTAT5 signaling, and these phenotypes could be reversed with pharmacological inhibition and genetic knockout. We also observed that inhibition of BMX in primary FLT3-mutated AML samples decreased chemokine secretion and enhanced the activity of gilteritinib. Collectively, these findings indicate a crucial role for microenvironment-mediated factors modulated by BMX in the escape from targeted therapy and have implications for the development of novel therapeutic interventions to restore sensitivity to gilteritinib.
Topics: Aniline Compounds; Humans; Leukemia, Myeloid, Acute; Mutation; Protein-Tyrosine Kinases; Pyrazines; Tumor Microenvironment; fms-Like Tyrosine Kinase 3
PubMed: 35797240
DOI: 10.1182/bloodadvances.2022007952 -
Biomolecules Nov 2021Pyrazines are organic compounds with a varied, intense aroma of roasted nuts, occasionally with hints of baked potatoes, almonds, and others. As a result, they are used...
Pyrazines are organic compounds with a varied, intense aroma of roasted nuts, occasionally with hints of baked potatoes, almonds, and others. As a result, they are used in the food industry as food flavorings. Biosynthesis of pyrazines using microorganisms in environmentally friendly conditions is an alternative to chemical synthesis. However, screening is required to isolate efficient producer strains for efficient biosynthesis of this compound. The study's goal was to assess the ability of cultures isolated from natto (fermented soybeans) to biosynthesize a broad range of alkylpyrazines. isolated cultures were found to be capable of producing 2-methylpyrazine, 2,3-dimethylpyrazine, 2,5-dimethylpyrazine, 2,6-dimethylpyrazine, 2,3,5-trimethylpyrazine, and 2,3,5,6-tetramethylpyrazine. As a result of the screening, two cultures of capable of producing alkylpyrazines were isolated. At a total concentration of 3261 µg/L, the BcP4 strain primarily produced 2-methylpyrazine (690 µg/L), 2,3-dimethylpyrazine (680 µg/L), and 2,6-dimethylpyrazine (1891 µg/L). At a total concentration of 558 mg/L, the BcP21 strain produced 2,5-dimethylpyrazine (4.5 mg/L), 2,3,5-trimethylpyrazine (52.6 mg/L), and 2,3,5,6-tetramethylpyrazine (501.1 mg/L). The results show that different strains are predisposed to produce different alkylpyrazines.
Topics: Bacillus; Fermentation; Pyrazines; Glycine max
PubMed: 34827734
DOI: 10.3390/biom11111736 -
Bioorganic & Medicinal Chemistry Letters Sep 2022Multidrug-resistant (MDR) Gram-negative bacteria are an urgent and rapidly spreading threat to human health with limited treatment options. Previously, we discovered a...
Multidrug-resistant (MDR) Gram-negative bacteria are an urgent and rapidly spreading threat to human health with limited treatment options. Previously, we discovered a novel [1,2,5]oxadiazolo[3,4-b]pyrazine-containing compound (1) that selectively re-sensitized a variety of MDR Gram-negative bacteria to colistin, one of the last-resort antibiotic. Herein, we report the structure-activity relationship studies of compound 1 that led to the discovery of several more potent and/or less toxic resistance-modifying agents (RMAs). Further evaluation of these RMAs showed that they were effective in a wide range of MDR bacteria. These results demonstrated these compounds as a novel class of RMAs and may be further developed as therapeutic agents.
Topics: Anti-Bacterial Agents; Drug Resistance, Multiple, Bacterial; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Polymyxins; Pyrazines; Structure-Activity Relationship
PubMed: 35788034
DOI: 10.1016/j.bmcl.2022.128878 -
Molecules (Basel, Switzerland) Nov 2021Pyrazines (1,4-diazirines) are an important group of natural products that have tremendous monetary value in the food and fragrance industries and can exhibit a wide...
Pyrazines (1,4-diazirines) are an important group of natural products that have tremendous monetary value in the food and fragrance industries and can exhibit a wide range of biological effects including antineoplastic, antidiabetic and antibiotic activities. As part of a project investigating the secondary metabolites present in understudied and chemically rich Actinomycetes, we isolated a series of six pyrazines from a soil-derived sp. GA3-008, four of which are new. Here we describe the structures of lentzeacins A-E (, , and ) along with two known analogues ( and ) and the porphyrin zincphyrin. The structures were determined by NMR spectroscopy and HR-ESI-MS. The suite of compounds present in sp. includes 2,5-disubstituted pyrazines (compounds , , and ) together with the new 2,6-disubstituted isomers (compounds , and ), a chemical class that is uncommon. We used long-read Nanopore sequencing to assemble a draft genome sequence of sp. which revealed the presence of 40 biosynthetic gene clusters. Analysis of classical di-modular and single module non-ribosomal peptide synthase genes, and cyclic dipeptide synthases narrows down the possibilities for the biosynthesis of the pyrazines present in this strain.
Topics: Actinomycetales; Biosynthetic Pathways; Carbon-13 Magnetic Resonance Spectroscopy; Genome, Bacterial; Multigene Family; Peptide Synthases; Proton Magnetic Resonance Spectroscopy; Pyrazines; Soil Microbiology; Substrate Specificity
PubMed: 34885778
DOI: 10.3390/molecules26237197 -
Molecules (Basel, Switzerland) Dec 20193-Alkyl-2-methoxypyrazines (MPs) contribute to the herbaceous flavor characteristics of wine and are generally considered associated with poor-quality wine. To control... (Review)
Review
3-Alkyl-2-methoxypyrazines (MPs) contribute to the herbaceous flavor characteristics of wine and are generally considered associated with poor-quality wine. To control the MPs in grapes and wine, an accurate understanding of MP metabolism is needed. This review covers factors affecting people in the perception of MPs. Also, the history of -methyltransferases is revisited, and the present review discusses the MP biosynthesis, degradation, and biochemical regulation. We propose the existence of a cycle between MPs and 3-alkyl-2-hydropyrazines (HPs), which proceeds via -(de)methylation steps. This cycle governs the MP contents of wines, which make the cycle the key participant in MP regulation by genes, environmental stimuli, and microbes. In conclusion, a comprehensive metabolic pathway on which the HP-MP cycle is centered is proposed after gaining insight into their metabolism and regulation. Some directions for future studies on MPs are also proposed in this paper.
Topics: Catalysis; Fermentation; Gene Expression Regulation; Metabolic Networks and Pathways; Methylation; Molecular Structure; Odorants; Olfactory Perception; Pyrazines; Smell; Vitis; Wine
PubMed: 31888183
DOI: 10.3390/molecules24244598 -
Clinical Pharmacokinetics Aug 2016The 2014-2015 outbreak of Ebola virus disease is the largest epidemic to date in terms of the number of cases, deaths, and affected areas. In October 2015, no antiviral... (Review)
Review
The 2014-2015 outbreak of Ebola virus disease is the largest epidemic to date in terms of the number of cases, deaths, and affected areas. In October 2015, no antiviral agents had proven antiviral efficacy in patients. However, in September 2014, the World Health Organization inventoried and has since regularly updated a list of potential drug candidates with demonstrated antiviral efficacy in in vitro or animal models. This includes agents belonging to various therapeutic classes, namely direct antiviral agents (favipiravir and BCX4430), a combination of antibodies (ZMapp), type I interferons, RNA interference-based drugs (TKM-Ebola and AVI-7537), and anticoagulant drugs (rNAPc2). Here, we review the pharmacokinetic and pharmacodynamic information presently available for these drugs, using data obtained in healthy volunteers for pharmacokinetics and data obtained in human clinical trials or animal models for pharmacodynamics. Future studies evaluating these drugs in clinical trials are critical to confirm their efficacy in humans, propose appropriate doses, and evaluate the possibility of treatment combinations.
Topics: Adenine; Adenosine; Amides; Animals; Antiviral Agents; Disease Outbreaks; Ebolavirus; Healthy Volunteers; Hemorrhagic Fever, Ebola; Humans; Models, Animal; Purine Nucleosides; Pyrazines; Pyrrolidines
PubMed: 26798032
DOI: 10.1007/s40262-015-0364-1