本文選題：白楊素 + 衍生物�。� 參考：《南華大學》2014年碩士論文

【摘要】：目的以白楊素為先導化合物，，設計、合成白楊素氨基酸類化合物，并初步探討其抗癌活性及作用機制，以期獲得高效、低毒、選擇性好的抗癌先導化合物，為探索和開發(fā)新的抗癌藥物提供理論依據(jù)。 方法通過鹵代、水解、縮合等化學反應對白楊素進行結(jié)構(gòu)改造；采用四甲基偶氮唑藍(MTT)法評價合成的白楊素衍生物對人胃癌細胞MGC-803和人肝癌細胞HepG2的增殖抑制作用；根據(jù)初步的細胞增殖實驗結(jié)果，采用流式細胞術(flowcytometry，F(xiàn)CM)檢測部分活性較好的衍生物對人胃癌細胞MGC-803的凋亡效應；通過Western blot探討可能的分子機制。 結(jié)果本文合成了不同系列的28個白楊素衍生物，其中22個化合物未見文獻報道。所有目標化合物及相關中間體通過熔點(M.P.)、核磁共振(NMR)以及高分辨率質(zhì)譜(ESI-TOF-MS)等手段進行結(jié)構(gòu)確證�；衔锏募毎鲋硨嶒灲Y(jié)果表明，與陽性藥物順鉑（cisplatin，DDP）及母體化合物白楊素相比，多數(shù)合成的白楊素衍生物對MGC-803、HepG2細胞的增殖具有良好的抑制作用，其中化合物N-[4-(5-羥基-2-苯基-4H-苯并吡喃酮-7-氧基)丁�；鵠異亮氨酸甲酯(20)對MGC-803細胞表現(xiàn)出比陽性對照更好的抑制作用。FCM和Western blot實驗結(jié)果顯示，化合物20能誘導MGC-803細胞凋亡、下調(diào)細胞中Bcl-xl蛋白表達以及上調(diào)Bax蛋白表達，且呈劑量依賴性。 結(jié)論本課題設計合成了不同系列結(jié)構(gòu)新型的白楊素衍生物，拓展了白楊素衍生物的研究范疇；初步完成了所合成的白楊素衍生物的細胞增殖抑制作用的評價，并探討其發(fā)揮抗癌作用的可能機制，為進一步設計開發(fā)具有誘導腫瘤細胞凋亡效應的新藥提供思路。
[Abstract]:Objective to design and synthesize the amino acid compounds of aspen with poplar as a leading compound, and to explore its anticancer activity and mechanism so as to obtain high efficiency, low toxicity and good selectivity. To provide theoretical basis for exploring and developing new anticancer drugs. Methods by halogenation, hydrolysis, condensation and other chemical reactions, the structural modification of alginine was carried out, and the inhibitory effects of the synthesized derivatives on the proliferation of human gastric cancer cell line MGC-803 and human hepatocellular carcinoma cell line HepG2 were evaluated by MTT assay. According to the preliminary results of cell proliferation, flow cytometry (FCM) was used to detect the apoptotic effect of some active derivatives on human gastric cancer cell line MGC-803, and the possible molecular mechanism was explored by Western blot. Results 28 different series of white poplar derivatives were synthesized in this paper, 22 of which were not reported in literature. The structures of all the target compounds and their related intermediates were confirmed by means of melting point (M. P.), NMR and high resolution mass spectrometry (ESI-TOF-MS). The results of cell proliferation assay showed that compared with cisplatin (cisplatin DDP) and its parent compound, most of the synthesized derivatives had a good inhibitory effect on the proliferation of MGC-803 HepG2 cells. Among them, compound N- [4- (5-hydroxy-2-phenyl-4H-benzopyranone -7oxy) butyryl] methyl ester (20) showed a better inhibitory effect on MGC-803 cells than the positive control. FCM and Western blot experiments showed that compound 20 could induce apoptosis of MGC-803 cells. The expression of Bcl-xl protein and the expression of Bax protein were down-regulated in a dose-dependent manner. Conclusion in this paper, we have designed and synthesized new series of white salicyrin derivatives with different structures, expanded the scope of research on them, and preliminarily completed the evaluation of the inhibitory effect of the synthesized derivatives on cell proliferation. The possible mechanism of its anticancer effect was also discussed, which provided ideas for the further design and development of new drugs with the effect of inducing apoptosis of tumor cells.
【學位授予單位】：南華大學
【學位級別】：碩士
【學位授予年份】：2014
【分類號】：R914;R96

【參考文獻】

相關期刊論文 前1條

1 康帥濤;李曉東;許環(huán)軍;孫鐵民;黃健;王金輝;;黃酮及其衍生物的高效合成和抗腫瘤活性[J];沈陽藥科大學學報;2011年11期

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