- Identification of Pyruvate Carboxylase as the Cellular Target of Natural Bibenzyls with Potent Anticancer Activity against Hepatocellular Carcinoma via Metabolic Reprogramming
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Cancer cell proliferation in some organs often depends on conversion of pyruvate to oxaloacetate via pyruvate carboxylase (PC) for replenishing the tricarboxylic acid cycle to support biomass production. In this study, PC was identified as the cellular target of erianin using the photoaffinity labeling-click chemistry-based probe strategy. Erianin potently inhibited the enzymatic activity of PC, which mediated the anticancer effect of erianin in human hepatocellular carcinoma (HCC). Erianin modulated cancer-related gene expression and induced changes in metabolic intermediates. Moreover, erianin promotes mitochondrial oxidative stress and inhibits glycolysis, leading to insufficient energy required for cell proliferation. Analysis of 14 natural analogs of erianin showed that some compounds exhibited potent inhibitory effects on PC. These results suggest that PC is a cellular target of erianin and reveal the unrecognized function of PC in HCC tumorigenesis; erianin along with its analogs warrants further development as a novel therapeutic strategy for the treatment of HCC.
- Sheng, Yuwen,Chen, Yuwen,Zeng, Zhongqiu,Wu, Wenbi,Wang, Jing,Ma, Yuling,Lin, Yuan,Zhang, Jichao,Huang, Yulan,Li, Wenhua,Zhu, Qiyu,Wei, Xiao,Li, Suiyan,Wisanwattana, Wisanee,Li, Fu,Liu, Wanli,Suksamrarn, Apichart,Zhang, Guolin,Jiao, Wei,Wang, Fei
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supporting information
p. 460 - 484
(2022/01/03)
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- Multicomponent cascade cycloaddition involving tropone, allenoate, and isocyanide: A rapid access to a 7,6,5-fused tricyclic skeleton
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Multicomponent cascade cycloaddition of tropone, allenoate, and isocyanide has been disclosed. This method allows for the rapid construction of a highly unusual tricyclic skeleton in an efficient manner. The proposed transformation proceeds through [8 + 2 + 1] cycloaddition, [1,5]-H shift, and cyclization followed by an alkoxy group migration process.
- Jia, Shuanglong,Su, Shikuan,Li, Chunju,Jia, Xueshun,Li, Jian
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p. 5604 - 5607
(2015/02/19)
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- Efficient one-pot synthesis of unsymmetrical gold(I) N-heterocyclic carbene complexes and their use as catalysts
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Eleven different gold(I) complexes of new NHC ligands were prepared in excellent yield, demonstrating the versatility of the new route to NHC complexes. While the influence of electronically different ligands on the synthesis of the catalysts was small, the catalytic activities of the products differed significantly.
- Hashmi, A. Stephen K.,Yu, Yang,Rominger, Frank
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p. 895 - 904
(2012/04/04)
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- Isocyanide-based multicomponent [2+2+1]-cycloaddition strategy to construct functionalized spirocyclic oxindoles
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Isocyanide-based three-component [2+2+1]-cycloaddition reactions from isocyanides, activated alkynes, and isatylidene malononitriles were investigated to provide a new access to spirocyclic oxindole with five-membered carbon rings. The displacement of isatylidene malononitrile with oxindolylideneacetate essentially results in opposite regioselectivity, which adds to its attractiveness. Georg Thieme Verlag Stuttgart ? New York.
- Jie, Haohua,Li, Jian,Li, Chunju,Jia, Xueshun
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p. 2274 - 2278
(2012/10/29)
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- A copper(I) isonitrile complex as a heterogeneous catalyst for azide-alkyne cycloaddition in water
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A structurally well-defined copper(I) isonitrile complex is shown to be an efficient, heterogeneous catalyst for the Huisgen azide-alkyne 1,3-dipolar cycloaddition under mild conditions in water. Notably, this catalyst can also be utilized in a three-component reaction of halides, sodium azide and alkynes to form 1,4-disubstituted 1,2,3-triazoles in high yields. Furthermore, it can be readily recovered by precipitation and filtration and recycled for at least five runs without significant loss of activity.(Figure Presented)
- Liu, Meina,Reiser, Oliver
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p. 1102 - 1105
(2011/04/24)
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- An improved approach for the synthesis of α,α-dialkyl glycine derivatives by the Ugi-Passerini reaction
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A general and simple strategy for routine peptide synthesis with α,α-dialkyl glycines taking advantage of the four-component Ugi-Passerini reaction is presented. The isonitrile required for the reaction can be relatively simple and its selection based on cost, as the group it generates is easily removed under acidic conditions; in addition, this removal is not visibly affected by the bulkiness of the α-alkyl groups. Being a good leaving group from the N-terminal amino group of the amino acid, 4-methoxybenzyl was the choice for the amine component of the reaction. The method is illustrated with the synthesis of a series of acyl derivatives of several α,α-dialkyl glycines. The preparation of the latter compounds is also reported.
- Costa, Susana P.G.,Maia, Hernani L.S.,Pereira-Lima, Silvia M.M.A.
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p. 1475 - 1479
(2007/10/03)
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