開發(fā)了一條合成天然產(chǎn)物Uncinine的新方法,基于此設(shè)計(jì)合成了一系列新型的丁烯內(nèi)酯衍生物.通過噻唑藍(lán)（MTT）法評(píng)價(jià)了目標(biāo)化合物對(duì)胃癌細(xì)胞的增殖抑制活性,分析了其構(gòu)效關(guān)系.其中,3-嗎啉甲基-4-（4-叔丁基苯基）亞基丁烯內(nèi)酯（9l）對(duì)MGC803的IC50為2.9μmol/L,對(duì)胃癌細(xì)胞MGC803、HGC27以及SGC7901具有明顯的選擇性增殖抑制作用,而對(duì)正常的胃粘膜上皮細(xì)胞GES1具有較小的毒性.初步的作用機(jī)制研究表明,化合物9l誘導(dǎo)胃癌細(xì)胞MGC803凋亡依賴Caspase 9/3激活. 

【文章來源】：有機(jī)化學(xué). 2020,40(01)北大核心SCICSCD

【文章頁數(shù)】：30 頁

【文章目錄】：
1 Introduction
2 Results and discussion
    2.1 Chemistry
    2.2 Biology
        2.2.1 Evaluation of antiproliferation on MGC803
        2.2.2 Caspase-dependent apoptosis was induced by compound 9l in MGC803 cells
3 Conclusions
4 Experimental
    4.1 Chemistry
        4.1.1 Synthesis of 3-(bromomethyl)furan-2(5H)-one(3)
        4.1.2 Synthesis of compounds 4 and 5
        4.1.3 Synthesis of uncinine(6)
        4.1.4 Synthesis of compounds 7a～7e
        4.1.5 General procedure for the synthesis of uncinine analogues 8a～8e
        4.1.6 General procedure for the synthesis of compounds 9a～9p
        4.1.7 Synthesis of(Z)-3-(4-(tert-butyl)benzylidene)-indolin-2-one(11)
        4.1.8 Synthesis of(Z)-3-(4-(tert-butyl)benzylidene)-1-((tetra-hydro-2H-pyran-4-yl)methyl)indolin-2-one(12)
    4.2 Biological evalution
        4.2.2 Cell lines and cultures
        4.2.3 Analysis of cell proliferation
        4.2.4 Apoptosis analysis
        4.2.5 Western blot analysis
        4.2.6 Statistical analysis
輔助材料(Supporting Information)
    新型丁烯內(nèi)酯衍生物的設(shè)計(jì)合成及誘導(dǎo)胃癌細(xì)胞凋亡研究


【參考文獻(xiàn)】：
期刊論文
[1]Recent advances in gastric cancer early diagnosis[J]. Laura Necula,Lilia Matei,Denisa Dragu,Ana I Neagu,Cristina Mambet,Saviana Nedeianu,Coralia Bleotu,Carmen C Diaconu,Mihaela Chivu-Economescu.  World Journal of Gastroenterology. 2019(17)
[2]新型5,6-二氫-6-烷基吡喃酮類衍生物的設(shè)計(jì)、合成及腫瘤細(xì)胞增殖抑制活性研究[J]. 徐海偉,賈世龍,謝曉平,羅姣,王樹.  有機(jī)化學(xué). 2017(04)



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