共查询到18条相似文献,搜索用时 297 毫秒
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2,5-二取代-1,3,4-噻二唑衍生物的一锅法合成、结构表征及生物活性研究 总被引:4,自引:0,他引:4
采用超声波辐射与相转移催化联用技术, 一锅法合成出了8个新的2-(1-萘乙酰氨基)-5-芳氨甲基-1,3,4-噻二唑化合物, 这种合成方法具有反应条件温和、反应时间较短、产率较高等特点. 新化合物的结构利用IR, 1H NMR, 13C NMR, 1D NOE, MS和元素分析进行了表征. 人环氧酶-2 (COX-2)活性抑制实验结果表明, 目标化合物5f对COX-2具有很强的抑制活性, 抑制率高达95.59%; 化合物5g对COX-2也具有一定的抑制活性. 目标化合物无抗惊厥活性. 相似文献
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本文通过5-(α-萘)-2H-四唑-2-乙酰肼(Ⅰ)与芳酰基异硫氰酸酯缩合制得16种新的1-[5-(α-萘)-2H-四唑-2-乙酰基]-4-芳酰基胺基硫脲(Ⅱ),(Ⅲ)在碱性催化条件下环化为3-[5-(α-萘)-2H-四唑-2-亚甲基]-4-芳酰基-1,2,4-三唑啉-5-硫酮(Ⅲ),化合物的结构经元素分析,IR、~1H NMR和MS鉴定,对化合物(Ⅲ)的质谱裂解进行分析,解释了化合物(Ⅱ)的环化方向,经初步筛选,发现个别化合物对小麦胚芽生长有促进作用。 相似文献
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以萘普生(NPX)为前体, 分别与芳基钌(Ru)、 锇(Os)及铱(Ir)二聚体反应制备了3个单核配合物[Ru(η 6-p-cymene)(NPX-bpy)Cl]Cl(1), [Os(η 6-p-cymene)(NPX-bpy)Cl]Cl(2)和[Ir(η 5-Cp *)·(NPX-bpy)Cl]Cl(3). 利用元素分析、 电喷雾质谱和核磁共振波谱对3个配合物的组成和结构进行了表征, 并研究了其细胞毒性. 结果表明, 3个配合物对几种肿瘤细胞株均无毒性(IC50>100 μmol/L), 仅配合物1对NB-4细胞有中等程度的毒性(IC50=45.2 μmol/L), 且毒性大于配合物2和3, 这可能与配合物1在细胞核内具有更高的富集量有关. 此外, 3个配合物均可有效抑制COX-2的表达, 保留了萘普生的抗炎性质, 实现了金属配合物抗癌及抗炎的多功能化应用. 相似文献
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报道了在室温,以CHC13为溶剂,NH4Cl为催化剂,醛、2-萘酚及氨基硫脲(物质的量比为2∶1∶1)通过一步多组份偶合反应有效地合成了一系列的2-萘酚类缩胺基硫脲化合物,均得到了较好的收率.所有目标化合物均通过熔点测定,并用质谱、红外光谱、核磁共振谱、元素分析对其结构进行确证. 相似文献
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2 萘胺 (1)在甲醇中与铜胺络合物 [x(CuCl2 )∶x(苄胺或乙醇胺 ) =2∶1]室温下反应得到产率为 74 %的 1,1′ 联 2 萘胺 (2 ) .在醋酸铜、硝酸铜或高氯酸铜的催化下 ,1在甲醇中被氧气氧化为 2 氨基 1,4 萘醌 4 2′ 萘亚胺 (3) ,产率86 % .用X ray单晶衍射证实 3的乙酰化产物结构为 2 乙酰氨基 1,4 萘醌 E 4 2′ 萘亚胺 (4) .循环伏安研究表明 ,铜 (II)化合物的氧化反应选择性与其还原峰电位有关 .电喷雾质谱的分析表明 1,2 萘醌 2 亚胺 (6 )是生成 3的中间体 相似文献
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Olivier Terrier Sbastien Dilly Andrs Pizzorno Dominika Chalupska Jana Humpolickova Even Boua Francis Berenbaum Stphane Quideau Bruno Lina Bruno Fve Frdric Adnet Michle Sabbah Manuel Rosa-Calatrava Vincent Marchal Julien Henri Anny Slama-Schwok 《Molecules (Basel, Switzerland)》2021,26(9)
There is an urgent need for specific antiviral treatments directed against SARS-CoV-2 to prevent the most severe forms of COVID-19. By drug repurposing, affordable therapeutics could be supplied worldwide in the present pandemic context. Targeting the nucleoprotein N of the SARS-CoV-2 coronavirus could be a strategy to impede viral replication and possibly other essential functions associated with viral N. The antiviral properties of naproxen, a non-steroidal anti-inflammatory drug (NSAID) that was previously demonstrated to be active against Influenza A virus, were evaluated against SARS-CoV-2. Intrinsic fluorescence spectroscopy, fluorescence anisotropy, and dynamic light scattering assays demonstrated naproxen binding to the nucleoprotein of SARS-Cov-2 as predicted by molecular modeling. Naproxen impeded recombinant N oligomerization and inhibited viral replication in infected cells. In VeroE6 cells and reconstituted human primary respiratory epithelium models of SARS-CoV-2 infection, naproxen specifically inhibited viral replication and protected the bronchial epithelia against SARS-CoV-2-induced damage. No inhibition of viral replication was observed with paracetamol or the COX-2 inhibitor celecoxib. Thus, among the NSAID tested, only naproxen combined antiviral and anti-inflammatory properties. Naproxen addition to the standard of care could be beneficial in a clinical setting, as tested in an ongoing clinical study. 相似文献
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A series of 4-(methylsulfonyl)aniline derivatives were synthesized in order to obtain new compounds as a potential anti-inflammatory agents with expected selectivity against COX-2 enzyme. In vivo acute anti-inflammatory activity of the final compounds 11-14 was evaluated in rat using an egg-white induced edema model of inflammation in a dose equivalent to 3 mg/Kg of diclofenac sodium. All tested compounds produced significant reduction of paw edema with respect to the effect of propylene glycol 50% v/v (control group). Moreover, the activity of compounds 11 and 14 was significantly higher than that of diclofenac sodium (at 3 mg/Kg) in the 120-300 minute time interval, while compound 12 expressed a comparable effect to that of diclofenac sodium in the 60-240 minute time interval time, and compound 13 showed a comparable effect to that of diclofenac sodium at all experimental times. The result of this study indicates that the incorporation of the 4-(methylsulfonyl)aniline pharamacophore into naproxen, indomethacine, diclofenac and mefanamic acid maintained their anti-inflammatory activity and may increase selectivity towards the COX-2 enzyme which will be confirmed in the future by assessing COX-2: COX-1 inhibitory ratios using a whole blood assay. 相似文献
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Catherine J. Feld Dr. Alice Johnson Dr. Zhiyin Xiao Dr. Kogularamanan Suntharalingam 《Chemistry (Weinheim an der Bergstrasse, Germany)》2020,26(61):14011-14017
We report the breast cancer stem cell (CSC) potency of two nickel(II)-3,4,7,8-tetramethyl-1,10-phenanthroline complexes, 1 and 3 , containing the non-steroidal anti-inflammatory drugs (NSAIDs), naproxen and indomethacin, respectively. The nickel(II) complexes, 1 and 3 kill breast CSCs and bulk breast cancer cells in the micromolar range. Notably, 1 and 3 display comparable or better potency towards breast CSCs than salinomycin, an established CSC-active agent. The complexes, 1 and 3 also display significantly lower toxicity towards non-cancerous epithelial breast cells than breast CSCs or bulk breast cancer cells (up to 4.6-fold). Mechanistic studies suggest that 1 and 3 downregulate cyclooxygenase-2 (COX-2) in breast CSCs and kill breast CSCs in a COX-2 dependent manner. Furthermore, the potency of 1 and 3 towards breast CSCs decreased upon co-treatment with necroptosis inhibitors (necrostatin-1 and dabrafenib), implying that 1 and 3 induce necroptosis, an ordered form of necrosis, in breast CSCs. As apoptosis resistance is a hallmark of CSCs, compounds like 1 and 3 , which potentially provide access to alternative (non-apoptotic) cell death pathways could hold the key to overcoming hard-to-kill CSCs. To the best of our knowledge, 1 and 3 are the first compounds to be associated to COX-2 inhibition and necroptosis induction in CSCs. 相似文献
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Dr. Suxing Jin Dr. Nafees Muhammad Yuewen Sun Yehong Tan Hao Yuan Dongfan Song Prof. Dr. Zijian Guo Prof. Dr. Xiaoyong Wang 《Angewandte Chemie (Weinheim an der Bergstrasse, Germany)》2020,132(51):23513-23521
Breast cancer (BC) is one of the most common malignancies in women and often accompanied by inflammatory processes. Cyclooxygenase-2 (COX-2) plays a vital role in the progression of BC, correlating with the expression of programmed death-ligand 1 (PD-L1). Overexpression of PD-L1 contributes to the immune escape of cancer cells, and its blockade would stimulate anticancer immunity. Two multispecific platinum(IV) complexes DNP and NP were prepared using non-steroidal antiinflammatory drug naproxen (NPX) as axial ligand(s) to inhibit the BC cells. DNP exhibited high cytotoxicity and antiinflammatory properties superior over NP, cisplatin and NPX; moreover, it displayed potent antitumor activity and almost no general toxicity in mice bearing triple-negative breast cancer (TNBC). Mechanistic studies revealed that DNP could downregulate the expression of COX-2 and PD-L1 in vitro and vivo, inhibit the secretion of prostaglandin, reduce the expression of BC-associated protein BRD4 and phosphorylation of extracellular signal-regulated kinases 1/2 (Erk1/2), and block the oncogene c-Myc in BC cells. These findings demonstrate that DNP is capable of intervening in inflammatory, immune, and metastatic processes of BC, thus presenting a new mechanism of action for anticancer platinum(IV) complexes. The multispecificity offers a special superiority for DNP to treat TNBC by combining chemotherapy and immunotherapy in one molecule. 相似文献
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将青风藤中23个有效化学成分与COX-2酶对接,有四个化合物具有较低的结合自由能,其中以青藤碱为最低.进一步将这四个化合物与COX-1酶对接,发现这四个化合物与COX-1酶结合能力较弱,预示这四个化合物具有选择性抑制COX-2酶的能力.对青藤碱和COX-2以及COX-1酶的结合模式进行分析,发现青藤碱主要结合于COX-2酶的S′口袋,而COX-1酶的S′结合口袋中第523号残基由COX-2酶中的Val523变成了体积较大的Ile523,使得COX-1酶的S′结合口袋相对COX-2酶的结合口袋要小,从而导致青藤碱分子不能进入COX-1酶S′结合口袋.这成功解释了青藤碱选择性抑制COX-2酶的原因,与早期有关文献报道的实验结果相吻合,充分表明了对接模型的合理性,青藤碱等化合物可作为设计COX-2酶选择性抑制剂的先导化合物. 相似文献
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Prof. Kenneth K. Laali Angela T. Zwarycz Nicholas Beck Dr. Gabriela L. Borosky Dr. Manabu Nukaya Prof. Gregory D. Kennedy 《ChemistryOpen》2020,9(8):822-834
In an effort to combine the anti-proliferative effect of CUR-BF2 and CUR compounds with anti-inflammatory benefits of non-steroidal anti-inflammatory drugs (NSAIDs), a library of the bis- and mono-NSAID/CUR-BF2 and NSAID/CUR conjugates were synthesized by coupling flufenamic acid, flurbiprofen, naproxen, indomethacin, and ibuprofen to diversely substituted hydroxy-benzaldehydes via an ester linkage, and by subsequent reaction with acetylacetone-BF2 to form the bis- and the mono-NSAID/CUR-BF2 adducts. Since conversion to NSAID/CUR by the previously developed decomplexation protocol showed limited success, a set of NSAID/CUR conjugates were independently prepared by directly coupling the NSAIDs with parent curcumin. The bis-NSAID/CUR-BF2 and bis-NSAID-CUR hybrids exhibited low cytotoxicity in NCI-60 assay, and in independent cell viability assay on colorectal cancer (CRC) cells (HCT116, HT29, DLD-1, RKO, SW837, CaCo2) and in normal CR cells (CCD841CoN). By contrast, the mono-naproxin and mono-flurbiprofen CUR-BF2 adducts exhibited remarkable anti-proliferative and apoptopic activity in NCI-60 assay most notably against HCT-116 (colon), OVCAR-3 (ovarian), and ACHN (renal) cells. Computational molecular docking calculations showed favorable binding energies to HER2, VEGFR2, BRAF, and Bcl-2 as well as to COX-1 and COX-2, which in several cases exceeded known inhibitors. The main interactions between the ligands and the proteins were hydrophobic, although several hydrogen bonds were also observed. A sub-set of six compounds that had exhibited little or no cytotoxicity were tested for their anti-inflammatory response with THP-1 human macrophages in comparison to parent NSAIDs or parent curcumin. 相似文献
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Li X Liu Z Zhang XF Wang LJ Zheng YN Yuan CC Sun GZ 《Molecules (Basel, Switzerland)》2008,13(8):1530-1537
A bioassay-guided in vitro screen has revealed that a 70% methanol extract of the leaves of Salix matsudana shows considerable inhibitory activity against cyclooxygenases (COX-1 and COX-2). A subsequent phytochemical study led to the isolation of a new flavonoid, matsudone A (1), together with five known flavonoids--luteolin (2), isoquercitrin (3), 7-methoxyflavone (4), luteolin 7-O-glucoside (5), 4',7-dihydroxyflavone (6)--and two phenolic glycosides, leonuriside A (7) and piceoside (8). Their structures were elucidated on the basis of extensive 1D- and 2D-NMR studies, high resolution ESI mass spectroscopic analyses and comparisons with literature data. The isolated compounds 1-8 were tested for their inhibitory activities against COX-1 and COX-2. Compounds 1, 5 and 6 were found to have potent inhibitory effect on COX-2 and compounds 3-5 exhibited moderate inhibition against COX-1. 相似文献