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Scientific Reports May 2024
Topics: Carbazoles; Antifungal Agents; Pyrazines; Hydrogen-Ion Concentration; Humans; Photosensitizing Agents
PubMed: 38750047
DOI: 10.1038/s41598-024-59804-y -
Drug Design, Development and Therapy 2024The Coronavirus disease 2019 (COVID-19) pandemic is one of the most considerable health problems across the world. Severe acute respiratory syndrome coronavirus 2... (Review)
Review
The Coronavirus disease 2019 (COVID-19) pandemic is one of the most considerable health problems across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the major causative agent of COVID-19. The severe symptoms of this deadly disease include shortness of breath, fever, cough, loss of smell, and a broad spectrum of other health issues such as diarrhea, pneumonia, bronchitis, septic shock, and multiple organ failure. Currently, there are no medications available for coronavirus patients, except symptom-relieving drugs. Therefore, SARS-CoV-2 requires the development of effective drugs and specific treatments. Heterocycles are important constituents of more than 85% of the physiologically active pharmaceutical drugs on the market now. Several FDA-approved drugs have been reported including molnupiravir, remdesivir, ritonavir, oseltamivir, favipiravir, chloroquine, and hydroxychloroquine for the cure of COVID-19. In this study, we discuss potent anti-SARS-CoV-2 heterocyclic compounds that have been synthesized over the past few years. These compounds included; indole, piperidine, pyrazine, pyrimidine, pyrrole, piperazine, quinazoline, oxazole, quinoline, isoxazole, thiazole, quinoxaline, pyrazole, azafluorene, imidazole, thiadiazole, triazole, coumarin, chromene, and benzodioxole. Both in vitro and in silico studies were performed to determine the potential of these heterocyclic compounds in the fight against various SARS-CoV-2 proteins.
Topics: Humans; Antiviral Agents; COVID-19 Drug Treatment; Heterocyclic Compounds; SARS-CoV-2; COVID-19
PubMed: 38737333
DOI: 10.2147/DDDT.S450499 -
Drug Design, Development and Therapy 2024Lung adenocarcinoma currently ranks the leading causes of cancer-related mortality worldwide. Many anti-inflammation herbs, like tetramethylpyrazine, have shown their...
PURPOSE
Lung adenocarcinoma currently ranks the leading causes of cancer-related mortality worldwide. Many anti-inflammation herbs, like tetramethylpyrazine, have shown their anti-tumor potentials. Here, we evaluated the role of a novel chalcone derivative of tetramethylpyrazine ((E) -1- (E) -1- (2-hydroxy-5-chlorophenyl) -3- (3,5,6-trimethylpyrazin-2-yl) -2-propen-1, HCTMPPK) in lung adenocarcinoma.
METHODS
The effects of HCTMPPK on cell proliferation, apoptosis, and invasion were investigated by in-vitro assays, including CCK-8, colony formation assay, flow cytometry, transwell assay, and wound-healing assay. The therapeutic potential of HCTMPPK in vivo was evaluated in xenograft mice. To figure out the target molecules of HCTMPPK, a network pharmacology approach and molecular docking studies were employed, and subsequent experiments were conducted to confirm these candidate molecules.
RESULTS
HCTMPPK effectively suppressed the proliferative activity and migration, as well as enhanced the apoptosis of A549 cells in a concentration-dependent manner. Consistent with this, tumor growth was inhibited by HCTMPPK significantly in vivo. Regarding the mechanisms, HCTMPPK down-regulated Bcl-2 and MMP-9 and up-regulating Bax and cleaved-caspase-3. Subsequently, we identified 601 overlapping DEGs from LUAD patients in TCGA and GEO database. Then, 15 hub genes were identified by PPI network and CytoHubba. Finally, MELK was verified to be the HCTMPPK targeted site, through the molecular docking studies and validation experiments.
CONCLUSION
Overall, our study indicates HCTMPPK as a potential MELK inhibitor and may be a promising candidate for the therapy of lung cancer.
Topics: Animals; Humans; Mice; A549 Cells; Antineoplastic Agents; Apoptosis; Cell Movement; Cell Proliferation; Chalcone; Dose-Response Relationship, Drug; Down-Regulation; Drug Screening Assays, Antitumor; Lung Neoplasms; Mice, Inbred BALB C; Mice, Nude; Molecular Docking Simulation; Molecular Structure; Neoplasms, Experimental; Pyrazines; Structure-Activity Relationship; Tumor Cells, Cultured
PubMed: 38737331
DOI: 10.2147/DDDT.S449139 -
International Journal of Molecular... Apr 2024Multiple myeloma is an incurable plasma cell malignancy. Most patients end up relapsing and developing resistance to antineoplastic drugs, like bortezomib. Antibiotic...
Multiple myeloma is an incurable plasma cell malignancy. Most patients end up relapsing and developing resistance to antineoplastic drugs, like bortezomib. Antibiotic tigecycline has activity against myeloma. This study analyzed tigecycline and bortezomib combination on cell lines and plasma cells from myeloma patients. Apoptosis, autophagic vesicles, mitochondrial mass, mitochondrial superoxide, cell cycle, and hydrogen peroxide were studied by flow cytometry. In addition, mitochondrial antioxidants and electron transport chain complexes were quantified by reverse transcription real-time PCR (RT-qPCR) or western blot. Cell metabolism and mitochondrial activity were characterized by Seahorse and RT-qPCR. We found that the addition of tigecycline to bortezomib reduces apoptosis in proportion to tigecycline concentration. Supporting this, the combination of both drugs counteracts bortezomib in vitro individual effects on the cell cycle, reduces autophagy and mitophagy markers, and reverts bortezomib-induced increase in mitochondrial superoxide. Changes in mitochondrial homeostasis and upregulation may account for some of these findings. These data not only advise to avoid considering tigecycline and bortezomib combination for treating myeloma, but caution on the potential adverse impact of treating infections with this antibiotic in myeloma patients under bortezomib treatment.
Topics: Bortezomib; Humans; Multiple Myeloma; Tigecycline; Mitochondria; Reactive Oxygen Species; Apoptosis; Cell Line, Tumor; Antineoplastic Agents; Autophagy; Mitophagy; Cell Cycle
PubMed: 38732105
DOI: 10.3390/ijms25094887 -
Foods (Basel, Switzerland) Apr 2024Longjing tea is favored by consumers due to its refreshing and delicate aroma, as well as its fresh and sweet flavor. In order to study the processing technology of...
Longjing tea is favored by consumers due to its refreshing and delicate aroma, as well as its fresh and sweet flavor. In order to study the processing technology of Longjing tea with 'Baiye 1' tea varieties, solid phase microextraction and gas chromatography-mass spectrometry were used to analyze the volatile components of Longjing tea in different process stages. The results revealed the identification of 275 aroma metabolites in the processing samples of Longjing tea. The sensory evaluation and principal component analysis revealed that the leaves of fresh (XY) and spreading (TF) were different from the leaves of first panning (YQ), second panning (EQ), final panning (HG), and fragrance enhancing (TX). The relative contents of geraniol (1199.95 and 1134.51), linalool (745.93 and 793.98), methyl salicylate (485.22 and 314.67), phenylethyl alcohol (280.14 and 393.98), 2-methylfuran (872.28 and 517.96), 2-butenal (56.01 and 154.60), and 2-hexenal (46.22 and 42.24), refreshing and floral substances in the XY and TF stages, were higher than other stages. The aroma contents of 2-methylfuran, furfural, 2-methyl-1-penten-3-one, 3-hexen-2-one, dodecane, hexanoyl hexanoate, 2,5-dimethyl-pyrazine, and methyl-pyrazine were found to be significantly positively correlated with the intensity of chestnut aroma. In conclusion, this study contributes to a better understanding of the composition and formation mechanism of chestnut-like aroma and provides new insights into the processing technology to improve the quality of albino green tea.
PubMed: 38731709
DOI: 10.3390/foods13091338 -
Molecules (Basel, Switzerland) Apr 2024The production of peanut oil in the industrial sector necessitates the utilization of diverse raw materials to generate consistent batches with stable flavor profiles,...
The production of peanut oil in the industrial sector necessitates the utilization of diverse raw materials to generate consistent batches with stable flavor profiles, thereby leading to an increased focus on understanding the correlation between raw materials and flavor characteristics. In this study, sensory evaluations, headspace solid-phase micro-extraction gas chromatography mass spectrometry (HS-SPME-GC-MS), odor activity value (OAV) calculations, and correlation analysis were employed to investigate the flavors and main contributing amino acids of hot-pressed oils derived from different peanut varieties. The results confirmed that the levels of alcohols, aldehydes, and heterocyclic compounds in peanut oil varied among nine different peanut varieties under identical processing conditions. The OAVs of 25 key aroma compounds, such as methylthiol, 3-ethyl-2,5-dimethylpyrazine, and 2,3-glutarone, exceeded a value of 1. The sensory evaluations and flavor content analysis demonstrated that pyrazines significantly influenced the flavor profile of the peanut oil. The concentrations of 11 amino acids showed a strong correlation with the levels of pyrazines. Notably, phenylalanine, lysine, glutamic acid, arginine, and isoleucine demonstrated significant associations with both pyrazine and nut flavors. These findings will provide valuable insights for enhancing the sensory attributes of peanut oil and selecting optimal raw peanuts for its production.
Topics: Amino Acids; Arachis; Odorants; Gas Chromatography-Mass Spectrometry; Peanut Oil; Volatile Organic Compounds; Flavoring Agents; Pyrazines; Solid Phase Microextraction; Taste; Hot Temperature
PubMed: 38731439
DOI: 10.3390/molecules29091947 -
Frontiers in Chemistry 2024Tetraphenylethene-based ligands with lowered symmetry are promising building blocks for the construction of novel luminescent metal-organic frameworks (MOFs). However,...
Tetraphenylethene-based ligands with lowered symmetry are promising building blocks for the construction of novel luminescent metal-organic frameworks (MOFs). However, few examples have been reported, and predicting the ligand conformation and the dimensionality of the resulting MOF remains challenging. In order to uncover how synthetic conditions and accessible ligand conformations may affect the resulting MOF structure, four new MOF structures were synthesized under solvothermal conditions using the meta-coordinated tetraphenylethene-based ligand -ETTC and paddlewheel SBUs composed of Co(II), Cu(II), and Zn(II). WSU-10 (WSU = Washington State University) is formed with either Zn or Cu comprising stacked psuedo-2D layers. The dimensionality of WSU-10 can be intentionally increased through the addition of pyrazine as a pillar ligand into the synthesis, forming the 3D structure WSU-11. The third structure, WSU-20, is formed by the combination of Zn or Co with -ETTC and is intrinsically 3D without the use of a pillar ligand; interestingly, this is the result of a distortion in the paddlewheel SBU. Finally, Cu was also found to form a new structure (WSU-12), which displays an -ETTC conformation unique from that found in the other isolated MOFs. Structural features are compared across the series and a mechanistic relationship between WSU-10 and -20 is proposed, providing insight into the factors that can encourage the generation of frameworks with increased dimensionality.
PubMed: 38725653
DOI: 10.3389/fchem.2024.1396123 -
Chemical Science May 2024Designing molecules with donor-acceptor-donor (D-A-D) architecture plays an important role in obtaining second near-infrared region (NIR-II, 1000-1700 nm) fluorescent...
Designing molecules with donor-acceptor-donor (D-A-D) architecture plays an important role in obtaining second near-infrared region (NIR-II, 1000-1700 nm) fluorescent dyes for biomedical applications; however, this always comes with a challenge due to very limited electronic acceptors. On the other hand, to endow NIR-II fluorescent dyes with combined therapeutic applications, trivial molecular design is indispensable. Herein, we propose a pyrazine-based planar electronic acceptor with a strong electron affinity, which can be used to develop NIR-II fluorescent dyes. By structurally attaching two classical triphenylamine electronic donors to it, a basic D-A-D module, namely Py-NIR, can be generated. The planarity of the electronic acceptor is crucial to induce a distinct NIR-II emission peaking at ∼1100 nm. The unique construction of the electronic acceptor can cause a twisted and flexible molecular conformation by the repulsive effect between the donors, which is essential to the aggregation-induced emission (AIE) property. The tuned intramolecular motions and twisted D-A pair brought by the electronic acceptor can lead to a remarkable photothermal conversion with an efficiency of 56.1% and induce a type I photosensitization with a favorable hydroxyl radical (OH˙) formation. Note that no additional measures are adopted in the molecular design, providing an ideal platform to realize NIR-II fluorescent probes with synergetic functions based on such an acceptor. Besides, the nanoparticles of Py-NIR can exhibit excellent NIR-II fluorescence imaging towards orthotopic 4T1 breast tumors in living mice with a high sensitivity and contrast. Combined with photothermal imaging and photoacoustic imaging caused by the thermal effect, the imaging-guided photoablation of tumors can be well performed. Our work has created a new opportunity to develop NIR-II fluorescent probes for accelerating biomedical applications.
PubMed: 38725487
DOI: 10.1039/d3sc06886b -
BMC Infectious Diseases May 2024Amidst limited influenza treatment options, evaluating the safety of Oseltamivir and Baloxavir Marboxil is crucial, particularly given their comparable efficacy. This...
BACKGROUND AND OBJECTIVES
Amidst limited influenza treatment options, evaluating the safety of Oseltamivir and Baloxavir Marboxil is crucial, particularly given their comparable efficacy. This study investigates post-market safety profiles, exploring adverse events (AEs) and their drug associations to provide essential clinical references.
METHODS
A meticulous analysis of FDA Adverse Event Reporting System (FAERS) data spanning the first quarter of 2004 to the fourth quarter of 2022 was conducted. Using data mining techniques like reporting odds ratio (ROR), proportional reporting ratio, Bayesian Confidence Propagation Neural Network, and Multiple Gamma Poisson Shrinkage, AEs related to Oseltamivir and Baloxavir Marboxil were examined. Venn analysis compared and selected specific AEs associated with each drug.
RESULTS
Incorporating 15,104 Oseltamivir cases and 1,594 Baloxavir Marboxil cases, Wain analysis unveiled 21 common AEs across neurological, psychiatric, gastrointestinal, dermatological, respiratory, and infectious domains. Oseltamivir exhibited 221 significantly specific AEs, including appendicolith [ROR (95% CI), 459.53 (340.88 ∼ 619.47)], acne infantile [ROR (95% CI, 368.65 (118.89 ∼ 1143.09)], acute macular neuroretinopathy [ROR (95% CI), 294.92 (97.88 ∼ 888.64)], proctitis [ROR (95% CI), 245.74 (101.47 ∼ 595.31)], and Purpura senile [ROR (95% CI), 154.02 (81.96 ∼ 289.43)]. designated adverse events (DMEs) associated with Oseltamivir included fulminant hepatitis [ROR (95% CI), 12.12 (8.30-17.72), n=27], ventricular fibrillation [ROR (95% CI), 7.68 (6.01-9.83), n=64], toxic epidermal necrolysis [ROR (95% CI), 7.21 (5.74-9.05), n=75]. Baloxavir Marboxil exhibited 34 specific AEs, including Melaena [ROR (95% CI), 21.34 (14.15-32.18), n = 23], cystitis haemorrhagic [ROR (95% CI), 20.22 (7.57-54.00), n = 4], ileus paralytic [ROR (95% CI), 18.57 (5.98-57.71), n = 3], and haemorrhagic diathesis [ROR (95% CI), 16.86 (5.43-52.40)), n = 3]. DMEs associated with Baloxavir Marboxil included rhabdomyolysis [ROR (95% CI), 15.50 (10.53 ∼ 22.80), n = 26].
CONCLUSION
Monitoring fulminant hepatitis during Oseltamivir treatment, especially in patients with liver-related diseases, is crucial. Oseltamivir's potential to induce abnormal behavior, especially in adolescents, necessitates special attention. Baloxavir Marboxil, with lower hepatic toxicity, emerges as a potential alternative for patients with liver diseases. During Baloxavir Marboxil treatment, focused attention on the occurrence of rhabdomyolysis is advised, necessitating timely monitoring of relevant indicators for those with clinical manifestations. The comprehensive data aims to provide valuable insights for clinicians and healthcare practitioners, facilitating an understanding of the safety profiles of these influenza treatments in real-world scenarios.
Topics: Humans; Dibenzothiepins; Triazines; United States; Oseltamivir; Antiviral Agents; United States Food and Drug Administration; Female; Male; Morpholines; Adult; Middle Aged; Pharmacovigilance; Adverse Drug Reaction Reporting Systems; Adolescent; Pyridones; Young Adult; Aged; Influenza, Human; Child; Triazoles; Thiepins; Pyrazines; Pyridines; Child, Preschool; Oxazines
PubMed: 38724914
DOI: 10.1186/s12879-024-09339-4 -
Food Chemistry: X Jun 2024The addition of baked Qingke improves the flavor profile of beer. In this study, beer was brewed using Qingke baked at various temperatures. The beer produced with...
The addition of baked Qingke improves the flavor profile of beer. In this study, beer was brewed using Qingke baked at various temperatures. The beer produced with Qingke baked at 180 °C achieved the highest sensory score (40/50), an alcohol content of 6.92% (/v), a total phenolic content of 446.42 mg/L, melanoidin concentration of 98.22 g/L, a color value of 10.88 EBC, and exhibited satisfactory antioxidant activity. Analysis of volatile compounds using HS-SPME-GC-MS revealed 48 compounds, of which esters accounted for 63% and alcohols accounted for 27% of the total content. The flavor profile of the beer varied across different baking temperatures. Pyrazines and aldehydes were predominantly present in samples baked at higher temperatures (T3, T4, and T5). Correlation analysis showed that the baking flavor in the beer was primarily correlated with 2, 5-dimethyl-pyrazine, trimethyl-pyrazine, phenylacetaldehyde, and ethyl 9-decenoate ( > 0.9).
PubMed: 38721384
DOI: 10.1016/j.fochx.2024.101394