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Inorganic Chemistry May 2024Phthalocyanines play fundamental roles as electron-acceptors in many different fields; thus, the study of structural features affecting electron-accepting properties of...
Phthalocyanines play fundamental roles as electron-acceptors in many different fields; thus, the study of structural features affecting electron-accepting properties of these macrocycles is highly desirable. A series of low-symmetry zinc(II) phthalocyanines, in which one, three, or four benzene rings were replaced for pyrazines, was prepared and decorated with electron-neutral (alkylsulfanyl) or strongly electron-withdrawing (alkylsulfonyl) groups to study the role of the macrocyclic core as well as the effect of peripheral substituents. Electrochemical studies revealed that the first reduction potential () is directly proportional to the number of pyrazine units in the macrocycle. Introduction of alkylsulfonyl groups had a very strong effect and resulted in a strongly electron-deficient macrocycle with = -0.48 V vs SCE (in THF). The efficiency of intramolecular-charge transfer (ICT) from the peripheral bis(2-methoxyethyl)amine group to the macrocycle was monitored as a decrease in the sum of Φ + Φ and correlated well with the determined values. The strongest quenching by ICT was observed for the most electron-deficient macrocycle. Importantly, an obvious threshold at -1.0 V vs SCE was observed over which no ICT occurs. Disclosed results may substantially help to improve the design of electron-donor systems based on phthalocyanines.
PubMed: 38679903
DOI: 10.1021/acs.inorgchem.4c00527 -
Leukemia Jun 2024The therapy of relapsed or refractory (r/r) mantle cell lymphoma (MCL) patients remains a major clinical challenge to date. We conducted a randomized, open-label,... (Randomized Controlled Trial)
Randomized Controlled Trial
The addition of bortezomib to rituximab, high-dose cytarabine and dexamethasone in relapsed or refractory mantle cell lymphoma-a randomized, open-label phase III trial of the European mantle cell lymphoma network.
The therapy of relapsed or refractory (r/r) mantle cell lymphoma (MCL) patients remains a major clinical challenge to date. We conducted a randomized, open-label, parallel-group phase-III trial hypothesizing superior efficacy of rituximab, high-dose cytarabine and dexamethasone with bortezomib (R-HAD + B) versus without (R-HAD) in r/r MCL ineligible for or relapsed after autologous stem cell transplant (ASCT). Primary endpoint was time to treatment failure (TTF), secondary endpoints included response rates, progression free survival, overall survival, and safety. In total, 128 of 175 planned patients were randomized to R-HAD + B (n = 64) or R-HAD (n = 64). Median TTF was 12 vs. 2.6 months (p = 0.045, MIPI-adjusted HR 0.69; 95%CI 0.47-1.02). Overall and complete response rates were 63 vs. 45% (p = 0.049) and 42 vs. 19% (p = 0.0062). A significant treatment effect was seen in the subgroup of patients >65 years (aHR 0.48, 0.29-0.79) and without previous ASCT (aHR 0.52, 0.28-0.96). Toxicity was mostly hematological and attributable to the chemotherapeutic backbone. Grade ≥3 leukocytopenia and lymphocytopenia were more common in R-HAD + B without differences in severe infections between both arms. Bortezomib in combination with chemotherapy can be effective in r/r MCL and should be evaluated further as a therapeutic option, especially if therapy with BTK inhibitors is not an option. Trial registration: NCT01449344.
Topics: Humans; Bortezomib; Lymphoma, Mantle-Cell; Antineoplastic Combined Chemotherapy Protocols; Female; Male; Dexamethasone; Aged; Middle Aged; Cytarabine; Rituximab; Neoplasm Recurrence, Local; Adult; Drug Resistance, Neoplasm; Survival Rate; Aged, 80 and over; Follow-Up Studies
PubMed: 38678093
DOI: 10.1038/s41375-024-02254-2 -
Spectrochimica Acta. Part A, Molecular... Aug 2024DNA is a key target for anticancer and antimicrobial drugs. Assessing the bioactivity of compounds involves in silico and instrumental studies to determine their...
DNA is a key target for anticancer and antimicrobial drugs. Assessing the bioactivity of compounds involves in silico and instrumental studies to determine their affinity for biomolecules like DNA. This study explores the potential of the switchSense technique in rapidly evaluating compound bioactivity towards DNA. By combining switchSense with computational methods and UV-Vis spectrophotometry, various bioactive compounds' interactions with DNA were analyzed. The objects of the study were: netropsin (as a model compound that binds in the helical groove), as well as derivatives of pyrazine (PTCA), sulfonamide (NbutylS), and anthraquinone (AQ-NetOH). Though no direct correlation was found between switchSense kinetics and binding modes, this research suggests the technique's broader utility in assessing new compounds' interactions with DNA. used as analytes whose interactions with DNA have not been yet fully described in the literature.
Topics: DNA; Spectrophotometry, Ultraviolet; Anthraquinones; Netropsin; Sulfonamides; Kinetics; Molecular Docking Simulation
PubMed: 38676984
DOI: 10.1016/j.saa.2024.124313 -
Viruses Apr 2024is the largest and most diverse genus in the family Peribunyaviridae. Orthobunyaviruses are widely distributed globally and pose threats to human and animal health....
is the largest and most diverse genus in the family Peribunyaviridae. Orthobunyaviruses are widely distributed globally and pose threats to human and animal health. Ebinur Lake virus (EBIV) is a newly classified Orthobunyavirus detected in China, Russia, and Kenya. This study explored the antiviral effects of two broad-spectrum antiviral drugs, favipiravir and ribavirin, in a BALB/c mouse model. Favipiravir significantly improved the clinical symptoms of infected mice, reduced viral titer and RNA copies in serum, and extended overall survival. The median survival times of mice in the vehicle- and favipiravir-treated groups were 5 and 7 days, respectively. Favipiravir significantly reduced virus titers 10- to 100-fold in sera at all three time points compared to vehicle-treated mice. And favipiravir treatment effectively reduced the virus copies by approximately 10-fold across the three time points, relative to vehicle-treated mice. The findings expand the antiviral spectrum of favipiravir for orthobunyaviruses in vivo.
Topics: Animals; Pyrazines; Amides; Antiviral Agents; Mice, Inbred BALB C; Mice; Disease Models, Animal; Viral Load; Female; Ribavirin; RNA Virus Infections
PubMed: 38675972
DOI: 10.3390/v16040631 -
Foods (Basel, Switzerland) Apr 2024Changes to the microbial community during pickled cucumber fermentation were studied using the 16S rDNA technique. The changes of volatile organic compounds (VOCs)...
Changes to the microbial community during pickled cucumber fermentation were studied using the 16S rDNA technique. The changes of volatile organic compounds (VOCs) during pickled cucumber fermentation were studied by gas chromatograph-ion mobility spectrometry. At the phylum level, and were the dominant flora in the natural fermentation group, and were the dominant flora in the added-bacteria fermentation group. At the generic level, the addition of led to changes in the community of the bacteria in the added-bacterial fermentation group and decreased the species abundance of other bacteria. In total, 75 volatile organic compounds were identified from naturally fermented pickled cucumber, and 60 volatile organic compounds were identified from fermented pickled cucumber with bacterial addition. The main metabolites were esters, aldehydes, acids, alcohols, ketones, alkanes, nitriles, and alkenes. These metabolites will bring their unique aroma components to the pickled cucumber. Metabolomic analysis of the O2PLS model showed that and were closely and positively correlated with nine alcohols, six esters, five aldehydes, four acids, three ketones, and one pyrazine. and show a close positive correlation with four kinds of alcohols, two kinds of esters, one kind of aldehyde, and one kind of nitrile.
PubMed: 38672946
DOI: 10.3390/foods13081275 -
Foods (Basel, Switzerland) Apr 2024Spirulina, a cyanobacterium widely used as a food supplement due to its high nutrient value, contains volatile organic compounds (VOCs). It is crucial to assess the...
Spirulina, a cyanobacterium widely used as a food supplement due to its high nutrient value, contains volatile organic compounds (VOCs). It is crucial to assess the presence of VOCs in commercial spirulina products, as they could influence sensory quality, various processes, and technological aspects. In this study, the volatile profiles of seventeen commercial spirulina food supplements were determined using headspace solid-phase microextraction (HS-SPME), coupled with gas chromatography-mass spectrometry (GC-MS). The identification of volatile compounds was achieved using a workflow that combined data processing with software tools and reference databases, as well as retention indices (RI) and elution order data. A total of 128 VOCs were identified as belonging to chemical groups of alkanes (47.2%), ketones (25.7%), aldehydes (10.9%), alcohols (8.4%), furans (3.7%), alkenes (1.8%), esters (1.1%), pyrazines (0.8%), and other compounds (0.4%). Major volatiles among all samples were hydrocarbons, especially heptadecane and heptadec-8-ene, followed by ketones (i.e., 4-(2,6,6-trimethyl-1-cyclohexen-1-yl)-3-buten-2-one, β-ionone, 2,2,6-trimethylcyclohexan-1-one), aldehydes (i.e., hexanal), and the alcohol oct-1-en-3-ol. Several volatiles were found in spirulina dietary supplements for the first time, including 6,10-dimethylundeca-5,9-dien-2-one (geranylacetone), 6,10,14-trimethylpentadecan-2-one, hept-2-enal, octanal, nonanal, oct-2-en-1-ol, heptan-1-ol, nonan-1-ol, tetradec-9-en-1-ol, 4,4-dimethylcyclohex-2-en-1-ol, 2,6-diethylpyrazine, and 1-(2,5-dimethylfuran-3-yl) ethanone. The methodology used for VOC analysis ensured high accuracy, reliability, and confidence in compound identification. Results reveal a wide variety of volatiles in commercial spirulina products, with numerous newly discovered compounds, prompting further research on sensory quality and production methods.
PubMed: 38672929
DOI: 10.3390/foods13081257 -
Food Chemistry: X Jun 2024Microwave technology offers a rapid and uniform heating method. This study investigated how microwave pretreatment affects the aroma precursors and flavor of fragrant...
Microwave technology offers a rapid and uniform heating method. This study investigated how microwave pretreatment affects the aroma precursors and flavor of fragrant rapeseed oils (FROs). Microwave pretreatment led to decreased levels of polyunsaturated fatty acids, sugars, protein-bound amino acids, and glucosinolates. Using gas chromatography-mass spectrometry, we identified 66 volatile compounds in the oil samples. Among these, based on odor activity values (OAV ≥ 1), we found 9 aldehydes, 1 ketone, 6 pyrazines, 1 isothiocyanate, and 7 nitriles as the key aroma-active compounds, contributing fatty-like, nutty-like, and pungent-like odors, respectively. The electronic nose results highlighted W5S and W1W as primary sensors for determining the flavor profiles of FROs. Notably, aroma-active pyrazines exhibited strong negative correlations with sucrose, cysteine, lysine, and isoleucine. This research provides essential insights for enhancing the aroma of FROs.
PubMed: 38665635
DOI: 10.1016/j.fochx.2024.101381 -
Cancer Reports (Hoboken, N.J.) Apr 2024Renal injury related to Waldenström macroglobulinemia (WM) occurs in approximately 3% of patients. Kidney biopsy is crucial to discriminate between distinct...
BACKGROUND
Renal injury related to Waldenström macroglobulinemia (WM) occurs in approximately 3% of patients. Kidney biopsy is crucial to discriminate between distinct histopathological entities such as glomerular (amyloidotic and non-amyloidotic), tubulo-interstitial and non-paraprotein mediated renal damage. In this context, disease characterization, management, relationship between renal, and hematological response have been poorly explored. We collected clinical, genetic and laboratory data of seven cases of biopsy-proven renal involvement by WM managed at our academic center and focused on three cases we judged paradigmatic discussing their histopathological patterns, clinical features, and therapeutic options.
CASE
In this illustrative case series, we confirm that serum creatinine levels and 24 h proteinuria are parameters that when altered should prompt the clinical suspicion of WM-related renal involvement, even if at present there are not precise cut-off levels recommending the execution of a renal biopsy. In our series AL Amyloidosis (n = 3/7) and tubulo-interstitial infiltration by lymphoma cells (n = 3/7) were the two more represented entities. BTKi did not seem to improve renal function (Case 1), while bortezomib-based regimens demonstrated a beneficial activity on the hematological and organ response, even when used as second-line therapy after chemoimmunotherapy (Case 3) and also with coexistence of anti-MAG neuropathy (Case 2). In case of poor response to bortezomib, standard chemoimmunotherapy (CIT), such as rituximab-bendamustine, represents an effective option (Case 1, 6, and 7). In our series, CIT generates durable responses more frequently in cases with amyloidogenic renal damage (Case 1, 5, and 7).
CONCLUSION
In this illustrative case series, we confirm that serum creatinine levels and 24 h proteinuria are parameters that when altered should prompt the clinical suspicion of WM-related renal involvement, even if at present there are not precise cut-off levels recommending the execution of a renal biopsy. Studies with higher numerosity are needed to better clarify the pathological and clinical features of renal involvement during WM and to determine the potential benefit of different therapeutic regimens according to the histopathological subtypes.
Topics: Humans; Waldenstrom Macroglobulinemia; Male; Aged; Female; Middle Aged; Kidney; Biopsy; Bortezomib
PubMed: 38662353
DOI: 10.1002/cnr2.2062 -
Journal of Molecular Modeling Apr 2024A complex supramolecular process involving electrostatic and dispersion interactions and asphaltene aggregation is associated with detrimental petroleum deposition and...
Density functional theory investigation of the contributions of π-π stacking and hydrogen bonding with water to the supramolecular aggregation interactions of model asphaltene heterocyclic compounds.
CONTEXT
A complex supramolecular process involving electrostatic and dispersion interactions and asphaltene aggregation is associated with detrimental petroleum deposition and scaling that pose challenges to petroleum recovery, transportation, and upgrading. The homodimers of seven heterocyclic model compounds, representative of moieties commonly found in asphaltene structures, were studied: pyridine, thiophene, furan, isoquinoline, pyrazine, thiazole, and 1,3-oxazole. The contributions of hydrogen bonding involving water bridges spanning between dimers and π-π stacking to the total interaction energy were calculated and analyzed. The distance between the planes of the aromatic rings is correlated with the π-π stacking interaction strength. All the dimerization reactions were exothermic, although not spontaneous. This was mostly modulated by the strength of the hydrogen bond of the water bridge and the π-π stacking interaction. Dimers bridged by two water molecules were more stable than those with additional water molecules or without any water molecule in the bridge. Energy decomposition analysis showed that the electrostatic and polarization components were the main stabilizing terms for the hydrogen bond interaction in the bridge, contributing at least 80% of the interaction energy in all dimers. The non-covalent interaction analysis confirmed the molecular sites that had the strongest (hydrogen bond) and weak (π-π stacking) attractive interactions. They were concentrated in the water bridge and in the plane between the aromatic rings, respectively.
METHODS
The density functional ωB97X-D with a dispersion correction and the Def2-SVP basis set were employed to investigate supramolecular aggregates incorporating heterocycles dimers with 0, 1, 2, and 3 water molecules forming a stabilizing bridge connecting the monomers. The non-covalent interactions were analyzed using the NCIplot software and plotted as isosurface maps using Visual Molecular Dynamics.
PubMed: 38656715
DOI: 10.1007/s00894-024-05922-3 -
Journal of Pharmaceutical and... Aug 2024Favipiravir is a broad-spectrum antiviral that is metabolised intracellularly into the active form, favipiravir ribofuranosyl-5'-triphosphate (F-RTP). Measurement of the...
Favipiravir is a broad-spectrum antiviral that is metabolised intracellularly into the active form, favipiravir ribofuranosyl-5'-triphosphate (F-RTP). Measurement of the intracellular concentration of F-RTP in mononuclear cells is a crucial step to characterising the pharmacokinetics of F-RTP and to enable more appropriate dose selection for the treatment of COVID-19 and emerging infectious diseases. The described method was validated over the range 24 - 2280 pmol/sample. Peripheral blood mononuclear cells (PBMCs) were isolated from whole blood and lysed using methanol-water (70:30, v/v) before cellular components were precipitated with acetonitrile and the supernatant further cleaned by weak anion exchange solid phase extraction. The method was found to be both precise and accurate and was successfully utilised to analyse F-RTP concentrations in patient samples collected as part of the AGILE CST-6 clinical trial.
Topics: Humans; Leukocytes, Mononuclear; Tandem Mass Spectrometry; Pyrazines; Amides; Antiviral Agents; COVID-19 Drug Treatment; Chromatography, Liquid; Solid Phase Extraction; SARS-CoV-2; COVID-19; Reproducibility of Results; Liquid Chromatography-Mass Spectrometry
PubMed: 38652938
DOI: 10.1016/j.jpba.2024.116155