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1.
Cell Death Differ ; 29(1): 230-245, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34453119

RESUMO

Mounting evidence indicates that immunogenic therapies engaging the unfolded protein response (UPR) following endoplasmic reticulum (ER) stress favor proficient cancer cell-immune interactions, by stimulating the release of immunomodulatory/proinflammatory factors by stressed or dying cancer cells. UPR-driven transcription of proinflammatory cytokines/chemokines exert beneficial or detrimental effects on tumor growth and antitumor immunity, but the cell-autonomous machinery governing the cancer cell inflammatory output in response to immunogenic therapies remains poorly defined. Here, we profiled the transcriptome of cancer cells responding to immunogenic or weakly immunogenic treatments. Bioinformatics-driven pathway analysis indicated that immunogenic treatments instigated a NF-κB/AP-1-inflammatory stress response, which dissociated from both cell death and UPR. This stress-induced inflammation was specifically abolished by the IRE1α-kinase inhibitor KIRA6. Supernatants from immunogenic chemotherapy and KIRA6 co-treated cancer cells were deprived of proinflammatory/chemoattractant factors and failed to mobilize neutrophils and induce dendritic cell maturation. Furthermore, KIRA6 significantly reduced the in vivo vaccination potential of dying cancer cells responding to immunogenic chemotherapy. Mechanistically, we found that the anti-inflammatory effect of KIRA6 was still effective in IRE1α-deficient cells, indicating a hitherto unknown off-target effector of this IRE1α-kinase inhibitor. Generation of a KIRA6-clickable photoaffinity probe, mass spectrometry, and co-immunoprecipitation analysis identified cytosolic HSP60 as a KIRA6 off-target in the IKK-driven NF-κB pathway. In sum, our study unravels that HSP60 is a KIRA6-inhibitable upstream regulator of the NF-κB/AP-1-inflammatory stress responses evoked by immunogenic treatments. It also urges caution when interpreting the anti-inflammatory action of IRE1α chemical inhibitors.


Assuntos
Endorribonucleases , Retículo Endoplasmático/metabolismo , Endorribonucleases/metabolismo , Humanos , Imidazóis , Morte Celular Imunogênica , Inflamação/metabolismo , Naftalenos , Pirazinas
2.
Pharmacol Res Perspect ; 10(3): e00929, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35593744

RESUMO

Verinurad is a selective inhibitor of uric acid transporter 1 (URAT1). Here, we assessed the safety, pharmacokinetics, and pharmacodynamics of verinurad + allopurinol and verinurad monotherapy in healthy participants. Studies 1 (NCT03836599) and 2 (NCT02608710) were randomized Phase 1 studies. In Study 1, 12 healthy Asian participants received 24 mg verinurad + 300 mg allopurinol or placebo, and 9 healthy Chinese participants received 12 mg verinurad + 300 mg allopurinol. In Study 2, 24 healthy non-Asian male participants received 12 mg verinurad. Safety analyses included assessment of adverse events (AEs). Pharmacokinetic parameters included maximum concentration (Cmax ) and area under plasma concentration-time curve (AUC) over 24 h (AUCτ ). Pharmacodynamic parameters included percentage change from baseline (day -1) in serum uric acid (sUA) and urinary uric acid (uUA). There were no serious AEs or deaths in either study. In Study 1, steady-state geometric mean (gCV%) Cmax and AUCτ values of verinurad after 7 days' dosing were 73.6 (29.0) ng/mL and 478 (18.4) ng·h/mL, respectively, in healthy Asian participants, and 42.0 (40.1) ng/mL and 264 (36.1) ng·h/mL, respectively, in healthy Chinese participants; in Study 2, gCV% values were 36.3 (36.5) ng/mL and 271 (31.0) ng·h/mL, respectively. sUA decreased and uUA excretion increased compared with baseline following verinurad + allopurinol (Study 1) or verinurad (Study 2). When accounting for dose, the steady-state pharmacokinetics of verinurad following multiple dosing were comparable between healthy Asian and Chinese participants and healthy non-Asian participants. Verinurad treatments were well tolerated, including at higher verinurad exposures than previously evaluated after repeated dosing.


Assuntos
Alopurinol , Ácido Úrico , Alopurinol/efeitos adversos , China , Humanos , Masculino , Naftalenos , Propionatos/efeitos adversos , Piridinas
3.
Environ Sci Technol ; 56(8): 4816-4827, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35384654

RESUMO

Secondary organic aerosols (SOAs) affect incoming solar radiation by interacting with light at ultraviolet and visible wavelength ranges. However, the relationship between the chemical composition and optical properties of SOA is still not well understood. In this study, the complex refractive index (RI) of SOA produced from OH oxidation of naphthalene in the presence of nitrogen oxides (NOx) was retrieved online in the wavelength range of 315-650 nm and the bulk chemical composition of the SOA was characterized by an online high-resolution time-of-flight mass spectrometer. In addition, the molecular-level composition of brown carbon chromophores was determined using high-performance liquid chromatography coupled to a photodiode array detector and a high-resolution mass spectrometer. The real part of the RI of the SOA increases with both the NOx/naphthalene ratio and aging time, likely due to the increased mean polarizability and decreased molecular weight due to fragmentation. Highly absorbing nitroaromatics (e.g., C6H5NO4, C7H7NO4, C7H5NO5, C8H5NO5) produced under higher NOx conditions contribute significantly to the light absorption of the SOA. The imaginary part of the RI linearly increases with the NOx/VOCs ratio due to the formation of nitroaromatic compounds. As a function of aging, the imaginary RI increases with the O/C ratio (slope = 0.024), mainly attributed to the achieved higher NOx/VOCs ratio, which favors the formation of light-absorbing nitroaromatics. The light-absorbing enhancement is not as significant with extensive aging as it is under a lower aging time due to the opening of aromatic rings by reactions.


Assuntos
Naftalenos , Óxidos de Nitrogênio , Aerossóis/química , Carbono/química , Oxirredução
4.
Nan Fang Yi Ke Da Xue Xue Bao ; 42(2): 201-206, 2022 Feb 20.
Artigo em Chinês | MEDLINE | ID: mdl-35365443

RESUMO

OBJECTIVE: To investigate the molecular mechanism by which a novel naphthalene allyl trifluoromethyl benzocyclopentanone XX0335 inhibits the proliferation and induces apoptosis of lung cancer A549 cells. METHODS: Lung cancer A549 cells were treated with 0.1% DMSO (control) or different concentrations (6.25, 12.5, and 25 µg/mL) of XX0335, and the changes in cell viability, cell cycle, proliferation and apoptosis were assessed with CCK-8 assay, EdU experiment, and flow cytometry. The effects of different concentrations of XX0335 on phosphorylation levels of proliferation-related proteins Akt, mTOR, Akt/mTOR and the expressions of cleaved PARP and cyclin D1 were determined using Western blotting. We also assessed the effect of XX0335 on tumor growth in a mouse model bearing A945 cell xenograft. RESULTS: Treatment with XX0335 reduced the viability of A549 cells in a dose-dependent manner (P < 0.01) and significantly inhibited cell proliferation (P < 0.001). Flow cytometry showed that XX0335 treatment promoted apoptosis of the cells (P < 0.01) and caused an obvious increase of the number of G1-phase cells. Compared with DMSO, XX0335 significantly inhibited the phosphorylation of Akt and mTOR, increased the expression of cleaved PARP, and lowered the protein expression of cyclin D1. In the tumor-bearing mouse models, injection of XX0335 significantly decreased the tumor volume (P < 0.01). CONCLUSION: XX0335 inhibits the proliferation, cycle and induces apoptosis of lung cancer A549 cells possibly by inhibiting the Akt/mTOR signal pathway.


Assuntos
Neoplasias Pulmonares , Células A549 , Animais , Apoptose , Proliferação de Células , Humanos , Neoplasias Pulmonares/metabolismo , Camundongos , Naftalenos/farmacologia
5.
Environ Sci Technol ; 56(9): 5520-5529, 2022 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-35417140

RESUMO

Intake from food is considered an important route of human exposure to polychlorinated naphthalenes. To our knowledge, several studies have quantified dietary exposure but only in European countries and measuring only a few of the 75 congeners. In addition, the influence of source diversity on human exposure has seldom been assessed. We analyzed 192 composite food samples composed of 17,280 subsamples from 24 provinces in China to measure the concentrations of polychlorinated naphthalenes and estimate their daily intake and potential health risks on a national scale. The estimated cancer risk was in the range of 6.8 × 10-8 to 4.6 × 10-7. We compared our findings for 75 congeners with reports in the literature that quantified only 12 congeners. We estimate that these 12 congeners contribute only approximately 4% to the total mass daily intake of polychlorinated naphthalenes and 70% to the total toxic equivalent quantity, indicating underestimation of dietary exposure. The contributions of combustion-associated congeners to the total concentrations of polychlorinated naphthalenes were in the range of 31-52%, suggesting that the ongoing unintentional release of these compounds from industrial thermal processes is an important factor in polychlorinated naphthalene contamination and human exposure in China.


Assuntos
Exposição Dietética , Bifenilos Policlorados , China , Dibenzofuranos Policlorados , Monitoramento Ambiental , Humanos , Indústrias , Naftalenos/toxicidade
6.
Int J Hyg Environ Health ; 242: 113971, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35472749

RESUMO

BACKGROUND: Refined coal tar sealant (RCTS) emulsions are used to seal the surface of asphalt pavement. Nine of the 22 polycyclic aromatic hydrocarbons (PAHs) evaluated in this study are classified as known, probable, or possible human carcinogens. Exposure assessment research for RCTS workers has not been published previously. OBJECTIVES: The overall objective of this study was to develop a representative occupational exposure assessment of PAH exposure for RCTS workers based on worksite surveys. The specific aims were to: 1) quantify full-shift airborne occupational exposures to PAHs among RCTS workers; 2) quantify workers' dermal exposures to PAHs; 3) quantify biomarkers of PAH exposure in workers' urine; 4) identify specific job titles associated with RCTS exposure; and 5) apply these results to a biological exposure index to assess risk of potential genotoxicity from occupational exposures. METHODS: A total of twenty-one RCTS workers were recruited from three companies. Personal and area air samples were collected using a modification of NIOSH Method 5515. Dermal exposure was assessed by hand and neck wipes before and after shifts. Twenty-two PAHs were quantified via gas chromatography-mass spectrometry selected ion monitoring. Internal dose was estimated by quantifying select PAH metabolites in pre- and post-shift urine samples using on-line solid phase extraction-high performance liquid chromatography-tandem mass spectrometry. RESULTS: PAH levels in the worker breathing zones were highest for naphthalene, acenaphthene, and phenanthrene, with geometric means of 52.1, 11.4, and 9.8 µg/m3, respectively. Hand wipe levels of phenanthrene, fluoranthene and pyrene were the highest among the 22 PAHs with geometric means of 7.9, 7.7, and 5.5 µg/cm2, respectively. Urinary PAH biomarkers for naphthalene, fluorene, phenanthrene, and pyrene were detected in all workers and were higher for post-shift samples than those collected pre-shift. Urinary concentrations of the metabolite 1-hydroxypyrene were greater than the American Conference of Governmental Industrial Hygienists (ACGIH) Biological Exposure Index (BEI) for this metabolite in 89 percent of post-shift samples collected on the final day of the work week or field survey. Statistically significances were found between concentrations of fluorene, naphthalene, and phenanthrene in the breathing zone of workers and their corresponding urinary PAH biomarkers. Workers were placed in two work place exposure groups: applicators and non-applicators. Applicators had higher total PAH concentrations in personal breathing zone (PBZ) air samples than non-applicators and were more likely to have post-shift hand wipe concentrations significantly higher than pre-shift concentrations. Concentrations of post-shift urinary biomarkers were higher, albeit not significantly, for applicators than non-applicators. CONCLUSIONS: The exposure results from RCTS worker samples cannot be explained by proximal factors such as nearby restaurants or construction. Air and skin concentration levels were substantially higher for RCTS workers than previously published levels among asphalt workers for all PAHs. PAH profiles on skin wipes were more consistent with RCTS sealant product than air samples. Last day post-shift urinary concentrations of 1-hydroxypyrene greatly exceeded the ACGIH BEI benchmark of 2.5 µg/L in 25 of 26 samples, which suggests occupational exposure and risk of genotoxicity. When pyrene and benzo[a]pyrene were both detected, concentration ratios from personal exposure samples were used to calculate the adjusted BEI. Concentrations of 1-hydroxypyrene exceeded the adjusted BEIs for air, hand wipes, and neck wipes in most cases. These results indicate the need to increase safety controls and exposure mitigation for RCTS workers.


Assuntos
Poluentes Ocupacionais do Ar , Alcatrão , Exposição Ocupacional , Fenantrenos , Hidrocarbonetos Policíclicos Aromáticos , Poluentes Ocupacionais do Ar/análise , Biomarcadores/urina , Alcatrão/análise , Monitoramento Ambiental/métodos , Fluorenos/análise , Humanos , Hidrocarbonetos/análise , Hidrocarbonetos/química , Naftalenos/análise , Exposição Ocupacional/análise , Fenantrenos/urina , Hidrocarbonetos Policíclicos Aromáticos/urina , Pirenos
7.
Biomed Pharmacother ; 149: 112881, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35367758

RESUMO

Mibefradil and NNC-55-0396, tetralol derivatives with a proven -ability to block T-type calcium channels in excitable cells, reduce cancer cell viability in vitro, causing cell death. Furthermore, they reduce tumor growth in preclinical models of Glioblastoma multiforme (GBM), a brain tumor of poor prognosis. Here we found that GBM cells treated with cytotoxic concentrations of NNC-55-0396 paradoxically increased cytosolic calcium levels through the activation of inositol triphosphate receptors (IP3R) and ER stress. We used pharmacological inhibitors and gene silencing to dissect the cell death pathway stimulated by NNC-55-0396 in GBM cell lines and biopsy-derived cultures. Calcium chelation or IP3R inhibition prevented NNC-55-0396-mediated cytotoxicity, indicating that ER calcium efflux is the cause of cell death. Upstream of calcium mobilization, NNC-55-0396 activated the IRE1α arm of the Unfolded Protein Response (UPR) resulting in the nuclear translocation of pro-apoptotic CHOP. Consistent with these findings, silencing IRE1α or JNK1 rescued the cell death elicited by NNC-55-0396. Therefore, we demonstrate that activation of IRE1α and calcium signaling accounts for the cytotoxicity of NNC-55-0396 in GBM cells. The delineation of the signaling pathway that mediates the abrupt cell death triggered by this compound can help the development of new therapies for GBM.


Assuntos
Glioblastoma , Apoptose , Benzimidazóis , Cálcio/metabolismo , Sinalização do Cálcio , Morte Celular , Ciclopropanos , Estresse do Retículo Endoplasmático/genética , Endorribonucleases/genética , Endorribonucleases/metabolismo , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Humanos , Naftalenos , Tetralonas , Resposta a Proteínas não Dobradas
8.
J Org Chem ; 87(9): 5904-5915, 2022 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-35388702

RESUMO

An efficient method for the preparation of arylnaphthalene lignans (ANLs) was developed, which is based on the Photo-Dehydro-Diels-Alder (PDDA) reaction. While intermolecular PDDA reactions turned out to be inefficient, the intramolecular variant using suberic acid as tether linking two aryl propiolic esters smoothly provided naphthalenophanes. The irradiations were performed with a previously developed annular continuous-flow reactor and UVB lamps. In this way, the natural products Alashinol D, Taiwanin C, and an unnamed ANL could be prepared.


Assuntos
Produtos Biológicos , Lignanas , Reação de Cicloadição , Ésteres , Naftalenos
9.
Chem Commun (Camb) ; 58(37): 5582-5585, 2022 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-35393986

RESUMO

Crystalline salts of the low solubility and low permeability drug naftopidil were investigated with mono-, di-, tri-, and tetrafluorobenzoic acids as coformers to show that 245TFBA (2,4,5-trifluorobenzoic acid) is the optimal salt with faster dissolution and high permeability, thereby opening the study of fluorinated coformers in pharmaceutical cocrystals and salts.


Assuntos
Sais , Cristalização , Naftalenos , Permeabilidade , Piperazinas , Sais/química , Solubilidade
10.
Chem Biol Interact ; 358: 109881, 2022 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-35307378

RESUMO

Stomach cancer causes the third-highest cancer-related deaths worldwide. Limited availability of anticancer measures with higher efficiency and low unwanted toxicities necessitates the development of better cancer chemotherapeutics. Naphthalene diimide (NDI) derivatives have gained significant attention owing to their excellent anticancer potential. We evaluated the anticancer properties of NDI derivatives, 1a and 2a in cancer cell lines and found that 1a showed higher efficacy as compared to 2a exhibiting a remarkable difference in activity upon single atom substitution of C with N. Particularly, NDI 1a showed potent inhibitory activity against gastric cancer cell line AGS with IC50 of 2.0 µM. NDI 1a induced remarkable morphological changes and reduced clonogenicity as well as the migratory ability of AGS cells. The reduction in AGS cell migration was mediated through inhibition of Tyr397 p-FAK dephosphorylation at focal adhesion points leading to enhanced attachment of cells at contact points. NDI 1a caused extensive DNA double-strand-breaks (DSBs) leading to activation of p53 and its transcriptional target p21. Reduced nuclear BRCA1 but enhanced nuclear p53BP1 foci formation upon 1a treatment suggests that DNA DSB repair is mediated through error-prone NHEJ which led to the accumulation of extensive DNA damage. Combinatorial effects mediated by interactions of 1a with double-stranded DNA through minor groove binding as well as induction of intracellular ROS exacerbated the loss of genomic integrity induced by 1a. NDI 1a mediated DNA damage-induced S phase arrest; however, cells experiencing extensive and irreparable DNA damage underwent mitochondrial apoptosis through downregulation of anti-apoptotic protein p21. Furthermore, proliferation inhibitory activity of 1a is also attributed to inhibition of ß-catenin/c-Myc axis in AGS cells with constitutively active ß-catenin pathway. In vivo toxicity analysis of 1a revealed minimal systemic toxicity suggesting that compound 1a is a safe and potential candidate for the development of gastric cancer chemotherapeutics.


Assuntos
Apoptose , Ciclo Celular , Dano ao DNA , Imidas , Naftalenos , Neoplasias Gástricas , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Humanos , Imidas/farmacologia , Naftalenos/farmacologia , Neoplasias Gástricas/genética , Neoplasias Gástricas/patologia , beta Catenina
11.
J Org Chem ; 87(6): 4323-4332, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35230123

RESUMO

Sarglaromatics A-E (1-5, respectively), five unprecedented naphthalene-like architecture-fused norlindenane sesquiterpene dimers, were discovered from the roots of Sarcandra glabra. The unique naphthalene core skeleton was obtained from classical lindenane [4 + 2] dimers via a free-radical-mediated C11-C11' bond formation reaction and 12'-decarboxylation. The highly fused octonary ring skeleton was elucidated by HRMS, NMR, ECD, quantum chemical calculations, and biogenetic inspiration. Compounds 1 and 2 showed significant anti-nonalcoholic steatohepatitis (NASH) activity by inhibiting lipid deposition in L02 cells.


Assuntos
Sesquiterpenos , Naftalenos , Raízes de Plantas/química , Polímeros , Sesquiterpenos/química
12.
Environ Sci Technol ; 56(6): 3340-3353, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35231168

RESUMO

We investigate the chemical composition of organic light-absorbing components, also known as brown carbon (BrC) chromophores, formed in a proxy of anthropogenic secondary organic aerosol generated from the photooxidation of naphthalene (naph-SOA) in the absence and presence of NOx. High-performance liquid chromatography equipped with a photodiode array detector and electrospray ionization high-resolution mass spectrometer is employed to characterize naph-SOA and its BrC components. We provide molecular-level insights into the chemical composition and optical properties of individual naph-SOA components and investigate their BrC relevance. This work reveals the formation of strongly absorbing nitro-aromatic chromophores under high-NOx conditions and describes their degradation during atmospheric aging. NOx addition enhanced the light absorption of naph-SOA while reducing wavelength-dependence, as seen by the mass absorption coefficient (MAC) and absorption Ångström exponent (AAE). Optical parameters of naph-SOA generated under low- and high-NOx conditions showed a range of values from MACOM 405nm ∼ 0.12 m2 g-1 and AAE300-450nm ∼ 8.87 (low-NOx) to MACOM 405nm ∼ 0.19 m2 g-1 and AAE300-450nm ∼ 7.59 (high-NOx), consistent with "very weak" and "weak" BrC optical classes, respectively. The weak-BrC class is commonly attributed to biomass smoldering emissions, which appear to have optical properties comparable with the naph-SOA. Molecular chromophores contributing to naphthalene BrC absorption were identified with substantial nitro-aromatics, indicating that these species may be used as source-specific markers of BrC related to the anthropogenic emissions.


Assuntos
Poluentes Atmosféricos , Carbono , Aerossóis/química , Poluentes Atmosféricos/análise , Biomassa , Carbono/química , Naftalenos
13.
J Fluoresc ; 32(3): 1189-1198, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35347531

RESUMO

A new probe (Z)-3-((naphthalen-1-ylmethylene)amino)phenol has been synthesized by condensation reaction between 1-naphthaldehyde and 3-aminophenol for the fluorescent sensing of Ce3+ by "on" mode and dichromate (Cr2O72-) by "off" mode. Metal ions-Ag+, Al3+, As3+, Ba2+, Ca2+, Cd2+, Ce4+, Co2+, Cr3+, Cr6+, Cu2+, Fe2+, Fe3+, Hg2+, K+, La+, Li+, Mg2+, Mn2+, Na+, Ni2+, Pb2+, Zn2+and anions Br-, C2O42-, CH3COO-, Cl-, CO32-, F-, H2PO4-, HCO3-, HF2-, HPO42-, I-, MnO4-, NO3-, OH-, S2-, S2O32-, SCN-, SO42- do not interfere. The limit of detection (LOD) for sensing Ce3+ and Cr2O72- ions are 1.286 × 10-7 M and 6.425 × 10-6 M, respectively.


Assuntos
Corantes Fluorescentes , Naftalenos , Aldeídos , Aminofenóis , Íons
14.
J Pharm Biomed Anal ; 214: 114715, 2022 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-35278811

RESUMO

Evocalcet is a calcimimetic for the treatment of secondary hyperparathyroidism. In the preparation of evocalcet, eleven process-related impurities were detected in the reaction solution of the last step at levels of 0.05%- 2.50% by a new HPLC method. Ten impurities were separated from the enriched mother liquor and synthesized directly. These impurities were characterized and identified by HRMS and NMR spectra and then coinjected with commercial products to confirm their retention times in HPLC. The possible formation pathways and synthetic methods of ten process-related impurities ware discussed in detail.


Assuntos
Hiperparatireoidismo Secundário , Cromatografia Líquida de Alta Pressão/métodos , Contaminação de Medicamentos , Humanos , Naftalenos , Pirrolidinas
15.
J Hazard Mater ; 432: 128693, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35338930

RESUMO

Naphthalene (NAP) has received increasing concern due to frequent detection in groundwater and harm to humans. In this study, FeS2 was selected as a novel catalyst to activate nano calcium peroxide (nCP) for NAP degradation. Batch experiments were conducted in a 250 mL glass reactor containing 0.1 mM NAP solution to investigate the effect of reagents dosage, pH, air conditions (with or without N2 purge), and different solution matrixes on NAP degradation. Scavenging tests, electron paramagnetic resonance (EPR) spectrum, and radical probe tests were conducted to identify the main radicals. Results indicated that over 96% NAP was removed in a wide pH range (3.0-9.0) within 180 min at optimal dosage of nCP = 1.0 mM and FeS2 = 5.0 g L-1 in nCP/FeS2 system. Aerobic condition was more beneficial to NAP degradation and the system could tolerate complex solution conditions. Moreover, HO• was determined to be responsible for NAP degradation. NAP degradation intermediates were detected by gas chromatography-mass spectrometry (GC-MS) and the possible degradation pathways were revealed. Finally, the efficient degradation of other organic pollutants confirmed the broad-spectrum reactivity of the nCP/FeS2 system. Overall, these findings strongly demonstrated the potential applicability of nCP/FeS2 system in remediating organic contaminated groundwater.


Assuntos
Água Subterrânea , Poluentes Químicos da Água , Humanos , Naftalenos , Oxirredução , Peróxidos , Poluentes Químicos da Água/análise
16.
Org Biomol Chem ; 20(15): 3174-3182, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35347333

RESUMO

The thermal tetradehydro-Diels-Alder (TDDA) reaction for the synthesis of polysubstituted aromatic compounds remains underestimated probably due to the harsh conditions and multiproduct results. Herein, a mild intramolecular TDDA reaction of aryldiyne compounds is presented with linear naphthalenes only, exhibiting good functional group tolerance. The reaction is easy to operate and amenable to multigram-scale synthesis. From the preliminary work, it was found that the mild conditions may be the key to the completely linear product in the reactions.


Assuntos
Naftalenos , Reação de Cicloadição
17.
J Org Chem ; 87(6): 4254-4262, 2022 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-35238199

RESUMO

Lyoniresinol and its derivatives are lignans which have been isolated from a plethora of plant species. In addition to exhibiting a range of interesting biological activities including anticancer, anti-inflammatory, antimicrobial, and others, these compounds have also been discovered in wines and spirits and shown to have gustatory effects in these alcoholic matrices. (+)-Lyoniresinol 1 is reported to impart a strong bitter taste while its enantiomer (-)-lyoniresnol 2 is tasteless. The first total asymmetric synthesis of both natural enantiomers (+)-1 and (-)-2 and their deuterated analogues (D4)-(+)-3 and (D4)-(-)-4 has been achieved, confirming the structure and stereochemistry of the natural products. The synthesized compounds can be utilized as internal standards in stable isotope dilution analysis for improving and optimizing the existing lyoniresinol quantitation methods in the future.


Assuntos
Anisóis , Vinho , Anisóis/análise , Naftalenos , Paladar , Vinho/análise
18.
Urologiia ; (1): 46-49, 2022 Mar.
Artigo em Russo | MEDLINE | ID: mdl-35274858

RESUMO

OBJECTIVE: to compare the efficacy of dapoxetine in treatment of primary and secondary premature ejaculation. MATERIALS AND METHODS: The study included 60 patients with premature ejaculation (PE). Depending on the form of premature ejaculation they were divided into two groups: 27 patients with primary PE (group 1) and 33 patients with secondary PE (group 2). Patients were recommended to take dapoxetine 30 mg 1 hour before intercourse. A follow-up visit was scheduled on day 30 after receiving the drug. The intravaginal ejaculation latency time (IELT) and the Premature ejaculation diagnostic tool (PEDT) score were evaluated before dapoxetine was given and after 30 days from the start of the study. The significance of differences between baseline and follow-up values were compared using Wilcoxons test. In both groups, the proportion of patients with an incomplete response (IELT less than 2 minutes, PEDT more than 10) to symptomatic therapy with dapoxetine was evaluated. The proportion of patients with incomplete response to therapy was compared using the chi-square test. RESULTS: The median IELT among all patients before starting therapy was 63 seconds (interquartile interval [IQR]: 28.75-94). After one month of therapy median IELT increased to 119 seconds (IQR: 58.75-321.75). Median PEDT score was 16 (IQR: 13-19) at baseline and 7 (IQR: 4-12) at follow-up. In group 1, the median IELT increased from 57 to 83 seconds (p = 0.02088), and in group 2, the median IELT increased from 70 to 173 seconds (p<0.00001). The mean PEDT score decreased to 7 in both groups (p<0.00001). Incomplete response to therapy was observed in 66.7% of patients in group 1 and in 39.4% of patients in group 2. The difference between two groups was statistically significant (p=0.035456). CONCLUSION: Symptomatic therapy with dapoxetine has a positive effect on the intravaginal ejaculation latency time and patient satisfaction in both primary and secondary premature ejaculation. However, the incidence of incomplete response to therapy is higher in patients with primary premature ejaculation, which may be due to characteristic differences in the pathogenesis of primary and secondary premature ejaculation.


Assuntos
Ejaculação Precoce , Inibidores de Captação de Serotonina , Benzilaminas/administração & dosagem , Benzilaminas/efeitos adversos , Benzilaminas/uso terapêutico , Ejaculação/efeitos dos fármacos , Humanos , Masculino , Naftalenos/administração & dosagem , Naftalenos/efeitos adversos , Naftalenos/uso terapêutico , Ejaculação Precoce/diagnóstico , Ejaculação Precoce/tratamento farmacológico , Inibidores de Captação de Serotonina/administração & dosagem , Inibidores de Captação de Serotonina/efeitos adversos , Inibidores de Captação de Serotonina/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
19.
Pak J Pharm Sci ; 35(1(Supplementary)): 259-265, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35228186

RESUMO

Present study was aimed to formulate solid dispersions (SD) of Dapoxetine (DAPO), a drug with low water solubility with the help of PVP-30, Ploxomer-180 (P-180) and ß-cyclodextrin (CD) by physical mixing to enhance the water solubility and dissolution of drug. Binary and Ternary solid dispersions were prepared with different ratios of drug and polymer and were further evaluated the effects of polymer at individual level as well as when used in combination. The solid dispersions were whitish in color, irregular in shape and have some rough surface when illustrated under SEM. Percentage yield of SDs ranged from 81-95% described the method was structured and significant. Solubility studies were carried out in 0.1N Hcl solution and was observed a remarkable increase in solubility of BSD 8, BSD 12 and TSD 6. Furthermore, the formulations were characterized by FTIR and PXRD. P-180 found an exceptional solubility promoter when used alone and in combination with CD as well. A remarkable enhance in Solubility and dissolution of DAPO was investigated in formulation prepared with ternary SD of Pol-180 and CD.


Assuntos
Benzilaminas/química , Portadores de Fármacos/química , Naftalenos/química , Polímeros/química , Inibidores de Captação de Serotonina/química , beta-Ciclodextrinas/química , Microscopia Eletrônica de Varredura , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier
20.
PLoS One ; 17(2): e0262829, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35176038

RESUMO

This ad hoc analysis of a previously conducted phase 3 head-to-head comparison study of evocalcet and cinacalcet in secondary hyperparathyroidism patients undergoing maintenance hemodialysis evaluated the efficacy and safety of combined once-daily oral evocalcet and intravenous vitamin D receptor activator treatment stratified by weekly vitamin D receptor activator dose (117, 45, and 91 patients in no, low [< 1.5 µg], and high [≥ 1.5 µg] dose groups, respectively). Effects of vitamin D receptor activator were assessed on the basis of intact parathyroid hormone, corrected calcium, phosphorus, and fibroblast growth factor-23 levels; percent changes from baseline; proportions of patients who achieved target intact parathyroid hormone, corrected calcium, and phosphorus at Weeks 28-30; and adverse drug reactions. Intact parathyroid hormone, corrected calcium, phosphorus, and fibroblast growth factor-23 levels decreased in all groups; phosphorus and fibroblast growth factor-23 levels remained high in the high dose group. In the low and high dose groups, greater proportions of patients achieved the corrected calcium target compared with the no dose group (p = 0.043). Ratios of intact-to-C-terminal fibroblast growth factor-23 decreased in all groups. In low and high dose groups, hypocalcemia was less common than in the no dose group (p = 0.014). Evocalcet with concomitant vitamin D receptor activator demonstrated benefits such that more patients achieved the corrected calcium target and exhibited decreased fibroblast growth factor-23 synthesis; the incidence of hypocalcemia also decreased. Clinical trial registration: ClinicalTrials.gov (NCT02549391) and JAPIC (JapicCTI-153013).


Assuntos
Calcimiméticos/uso terapêutico , Hiperparatireoidismo Secundário/tratamento farmacológico , Naftalenos/uso terapêutico , Pirrolidinas/uso terapêutico , Receptores de Calcitriol/agonistas , Método Duplo-Cego , Quimioterapia Combinada , Humanos , Hiperparatireoidismo Secundário/patologia , Masculino , Pessoa de Meia-Idade , Prognóstico
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