JOURNAL OF CATALYSIS
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2022
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IF 8.047
Xiaowen Sun,Qing-Nan Wang,Shengyang Wang,Pengfei Zhang,Zhendong Feng,Xianwen Zhang,Zhaochi Feng,Can Li
Photocatalytic selective oxidation of p -xylene with O 2 offers a mild pathway to synthesize p -methyl benzaldehyde ( p -MBA), which is one of the primary precursors in the manufacture of fine chemicals. Here, we report that Au/WO x /TiO 2 photocatalyst selectively catalyzes the oxidation of p -xylene to p -MBA with 88.6% selectivity at 1.0% conversion, the formation of CO x is suppressed to 0.8%. Kinetic experiments indicate that p -methylbenzyl alcohol and p -MBA are initial products. p -Methylbenzyl alcohol is further oxidized to form p -MBA, p -methylbenzyl acid and CO x ; p -MBA is further oxidized to p -methylbenzyl acid and CO x . On TiO 2 surface, p -methylbenzyl alcohol is more prone to directly combust to CO x by O 2 – . Loading of WO x can weaken the adsorption ability of p -methylbenzyl alcohol on the catalyst surface to avoid the combustion. Meanwhile, WO x and Au can facilitate the separation of photo-generated carriers to attain high activity and suppress the O 2 – formation to obtain high selectivity.
研究领域:
催化
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材料科学
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化学工程
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产品关联
DOI
高影响因子
BIOORGANIC CHEMISTRY
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2021
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IF 5.275
Peter A. Halim,Hanan H. Georgey,Mina Y. George,Ahmed M. El Kerdawy,Mona F. Said
Responding to the great demand of developing potent NSAIDs with an enhanced safety profile and reasonable selectivity, in the present study novel 4-fluorobenzamide derivatives were synthesized and screened for their anti-inflammatory and analgesic activities using carrageenan-induced rat paw edema method and acetic acid-induced abdominal writhing in mice, respectively. All the new target compounds except the carbamothioylhydrazine series ( 5a-d ), and the 4-fluorophenyl thiadiazolo derivative 6b showed promising anti-inflammatory activity ranged between 53.43 and 92.36% inhibition of edema (at 3 h) compared to the reference standard indomethacin (65.64%). All the newly synthesized compounds showed potent analgesic activity ranged between 71 and 100 % writhing protection compared to indomethacin (74.06%). Moreover, the most active compounds; the ester hybrids 2a,b , the thioureido quinazolinones 4b,c , and the thiadiazole congener 6a , showed promising gastric tolerability with ulcer index ranged between 0 and 6.60 compared to indomethacin (12.13). The thioureido quinazolinone derivatives 4b , c showed the most potent anti-inflammatory and analgesic activities with a remarkable gastric tolerability compared to the other derivatives. The 4-chlorophenyl derivative 4b is considered the most promising analogue showing 92.36% inhibition of edema, 100% writhing protection in analgesia testing, and a COX-2 selectivity index of 5.75 which was better than that of indomethacin and celecoxib standards (selectivity index = 0.27 and 4.55; respectively). Moreover, it showed an ulcer index equals zero with gastric acidity and mucin levels comparable to that of the control group indicating its minor effect on gastric cell physiology and its high tolerability. Molecular docking studies predicted the binding pattern of the newly synthesized compounds in COX-1 and COX-2 enzymes confirming the ability of the most active candidates to satisfy the structural features required for binding and rationalized their selectivity based on their docking binding patterns and scores. Furthermore, the newly synthesized 4-fluorobenzamide derivatives possess promising predicted pharmacokinetic properties indicated by calculating their key physicochemical parameters and absorption percentages.
研究领域:
药理学
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药物化学
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医学
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DOI
PubMed
高影响因子
JOURNAL OF ORGANIC CHEMISTRY
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2024
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IF 3.3
Huaiyuan Zhang,Nuo Xu,Botao Su,Jingren Zhang,Chongen Zhang,Zhiyuan Zhang,Binbin Guo,Shengjie Xu,Shouwei Wang,Rongping Tang
A metal-free, mild, and efficient method for the synthesis of amides has been developed from the amination of aldehydes with hydroxylamines promoted by TBAF·3H2O in the presence of KOH. Control experiments showed that the nitrone was the intermediate of this amination. By this method, a series of amides, biologically active compounds bebenil and a COX inhibitor were obtained in moderate to good yields.
研究领域:
有机化学
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合成化学
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药物化学
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DOI
PubMed
高影响因子
ChemMedChem
·
2023
·Vol. 18
·期 23
·e202300468
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IF 3.4
Jingjie Fang,Ziyi Shang,Kumaravel Kaliaperumal,Zhiran Ju,Fen-Er Chen
Graphical This study presents a design strategy, synthesis, and evaluation of balanced COX inhibitors derived from natural anti-inflammatory ascidian metabolites and celecoxib, highlighting their potential therapeutic value in the context of inflammation. The serious adverse effects caused by non-selective and selective cyclooxygenase-2 (COX-2) inhibitors remain significant concerns for current anti-inflammatory drugs. In this study, we present the design and synthesis of a novel series of celecoxib analogs incorporating a hydrazone linker, which were subjected to in silico analysis to compare their binding poses with those of clinically used nonsteroidal anti-inflammatory drugs (NSAIDs) against COX-1 and COX-2. The synthesized analogs were evaluated for their inhibitory activity against both COX enzymes, and compound 6 m , exhibiting potent balanced inhibition, was selected for subsequent in vitro anti-inflammatory assays. Treatment with 6 m effectively suppressed the NF-κB signaling pathway in lipopolysaccharide (LPS)-stimulated murine RAW264.7 macrophages, resulting in reduced expression of pro-inflammatory factors such as inducible nitric oxide synthase (iNOS), COX-2, tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), IL-1β, as well as decreased production of prostaglandin E 2 (PGE 2 ), nitric oxide (NO), and reactive oxygen species (ROS). However, 6 m has no effect on the MAPK signaling pathway. Therefore, due to its potent in vitro anti-inflammatory activity coupled with lack of cytotoxicity, 6 m represents a promising candidate for further development as a new lead compound targeting inflammation.
研究领域:
药理学
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药物化学
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炎症研究
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药物设计
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DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
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2025
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IF 8
Chuan Liang,Yang Chen,Yunzhe Ling,Peirun Li,Jiahao Liu,Xuantian Li,Yanhua Xu,Zhiying Liu
Non-steroidal anti-inflammatory drugs (NSAIDs), though designed to target specific molecular pathways, pose significant environmental risks to non-target organisms, particularly marine fish. This study investigated the toxicity mechanisms and adaptive responses to diclofenac (DCF) and meloxicam (MEX) during the early life stages (ELS) of Oryzias melastigma at environmentally relevant concentrations over a 31-day period. Mechanistic investigations of sub-lethal effects were conducted using Enzyme-Linked Immunosorbent Assay (ELISA), RNA sequencing (RNA-Seq) and quantitative PCR (qPCR). The results revealed that cyclooxygenase (COX) inhibition disrupted the renin-angiotensin system, leading to an accumulation of angiotensin II and cardiovascular developmental defects. Additionally, downregulation of the pla2 gene reduced substrates essential for COX enzyme activity, exacerbating the effects. Although NSAIDs are known to affect the digestive system, no significant effects on developmental factors were observed. RNA-Seq and qPCR analyses revealed an adaptive upregulation of key genes, including ace2 and cyp7a1 , involved in cardiovascular and metabolic regulation. Furthermore, 16S rRNA sequencing identified shifts in the microbial community, particularly in g_Rubritalea and g_Sphingomonas genera. Both the upregulated genes and the altered microbial taxa likely played a role in mitigating toxic effects and promoting homeostasis. Moreover, molecular docking suggested that MEX exhibited stronger sub-lethal effects than DCF, likely due to its higher binding affinity to COX. These findings provide valuable insights into NSAID toxicity mechanisms in marine fish, highlighting the importance of adaptive responses in countering environmental stress and underscoring the long-term ecological risks of chronic NSAID exposure.
研究领域:
海洋毒理学
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环境科学
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药理学
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分子生物学
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发育生物学
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生态毒理学
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微生物学
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生物信息学
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药物发现
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产品关联
DOI
PubMed
高影响因子
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