本文選題：金剛烷 + 缺氧誘導(dǎo)因子-1��； 參考：《長(zhǎng)春工業(yè)大學(xué)》2016年碩士論文

【摘要】：在腫瘤細(xì)胞缺氧的情況下,缺氧誘導(dǎo)因子-1(HIF-1)具有關(guān)鍵的調(diào)節(jié)作用,使腫瘤細(xì)胞順應(yīng)缺氧的環(huán)境。目前,缺氧誘導(dǎo)因子-1是抗腫瘤藥物研究的重要靶點(diǎn)。已經(jīng)發(fā)現(xiàn)了很多缺氧誘導(dǎo)因子-1抑制劑。其中,一些含金剛烷結(jié)構(gòu)的化合物可以作為缺氧誘導(dǎo)因子-1抑制劑。1.對(duì)化合物3-(4-羥苯基)金剛烷-1-羧酸的羧基部分和酚羥基部分進(jìn)行結(jié)構(gòu)修飾,合成了一類新型的含金剛烷結(jié)構(gòu)單元的3-(4-羥苯基)金剛烷-1-羧酸衍生物9個(gè),在合成這類化合物的過(guò)程中,合成了10個(gè)重要的中間體化合物。2.以化合物4-(1-金剛烷基)苯酚為骨架,對(duì)其苯酚環(huán)進(jìn)行結(jié)構(gòu)修飾,合成了新型的包含金剛烷結(jié)構(gòu)單元的4-(1-金剛烷基)苯酚衍生物4個(gè),在合成這類化合物的過(guò)程中,合成了7個(gè)中間體化合物。3.另外,以1-金剛烷羧酸為原料探究了具有金剛烷結(jié)構(gòu)單元的金剛烷羧酸衍生物的合成方法及實(shí)驗(yàn)條件。化合物的結(jié)構(gòu)是由核磁氫譜、碳譜、紅外光譜及質(zhì)譜確定的。利用熒光素酶報(bào)告基因的方法,檢測(cè)了這些化合物作為缺氧誘導(dǎo)因子-1抑制劑的潛能,得到了一些對(duì)缺氧誘導(dǎo)因子-1有抑制作用的抑制劑。并且,大部分合成的化合物在可以有效抑制缺氧誘導(dǎo)因子-1活性的濃度下,沒(méi)有明顯的細(xì)胞毒性。對(duì)合成的化合物進(jìn)行了結(jié)構(gòu)活性分析。在缺氧的條件下,具有吲哚基團(tuán)含金剛烷結(jié)構(gòu)單元的化合物20a可以作為肝癌細(xì)胞中缺氧誘導(dǎo)因子-1有效的抑制劑。而且,細(xì)胞毒性非常小(IC50=0.02μM)。這些化合物的合成可能會(huì)給新的抗腫瘤藥物的研發(fā)提供一些有價(jià)值的信息。
[Abstract]:Hypoxia-inducible factor-1 (HIF-1) plays a key role in regulating tumor cells to adapt to anoxic environment. At present, hypoxia-inducible factor-1 is an important target of anti-tumor drugs. A number of hypoxia inducible factor-1 inhibitors have been identified. Among them, some compounds with adamantane structure can be used as anoxic inducible factor-1 inhibitor. In this paper, the carboxyl and phenolic hydroxyl parts of the compound 3-O4-hydroxyphenyl) adamantine-1-carboxylic acid were modified, and a new class of derivatives of 3-O4-hydroxyphenyl) adamantine-1-carboxylic acid containing adamantane structure unit was synthesized. In the process of synthesizing these compounds, ten important intermediates. 2. 2 were synthesized. In this paper, the structure of the phenol ring was modified by the structure modification of the phenol ring of the compound 4-O1-adamantyl) phenol. Four new derivatives of phenol containing the adamantane structure unit were synthesized. In the process of synthesizing these compounds, four new derivatives were synthesized. Seven intermediates were synthesized. In addition, the synthetic method and experimental conditions of adamantane carboxylic acid derivatives with adamantane structure unit were studied using 1-adamantane carboxylic acid as raw material. The structure of the compound is determined by nuclear magnetic hydrogen spectrum, carbon spectrum, infrared spectrum and mass spectrometry. Luciferase reporter genes were used to detect the potential of these compounds as inhibitors of hypoxia inducible factor-1 (HIF-1), and some inhibitors were obtained to inhibit hypoxia inducible factor-1 (HIF-1). Moreover, most of the synthesized compounds have no obvious cytotoxicity at the concentration that can effectively inhibit the activity of hypoxia inducible factor-1 (HIF-1). The structure and activity of the synthesized compounds were analyzed. Under hypoxia condition, compounds with indolyl group containing adamantane structure unit can be used as effective inhibitors of hypoxia inducible factor-1 in hepatocellular carcinoma cells for 20a. Moreover, the cytotoxicity of IC50 / 0.02 渭 MN was very small. The synthesis of these compounds may provide valuable information for the development of new anti-tumor drugs.
【學(xué)位授予單位】：長(zhǎng)春工業(yè)大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2016
【分類號(hào)】：R914.5;R96;O657.63

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