本文選題：靛紅　切入點(diǎn)：抗腫瘤　出處：《天津科技大學(xué)》2014年碩士論文

【摘要】：靛紅又名吲哚滿(mǎn)二酮或2,3-吲哚醌,是存在于哺乳動(dòng)物組織和體液中的內(nèi)源性活性物質(zhì),它也存在于中藥青黛中。靛紅及其衍生物具有很好的抗腫瘤、抗菌、抗病毒和抗結(jié)核等活性。近年來(lái),以靛紅為母核結(jié)構(gòu)的衍生物的有機(jī)合成及其藥理活性研究受到越來(lái)越多人的關(guān)注。靛紅及其衍生物的吡咯環(huán)及苯環(huán)上可以發(fā)生多種類(lèi)型的化學(xué)反應(yīng),為其衍生物的研究提供了廣闊的空間。在以往合成的靛紅衍生物中,多數(shù)是在靛紅苯環(huán)上進(jìn)行一個(gè)位置取代基衍生合成,其它是在吡咯環(huán)上進(jìn)行反應(yīng)衍生取代,苯環(huán)上多位置取代靛紅的合成及生物活性的研究報(bào)道較少。本文設(shè)計(jì)合成了一系列在靛紅的4,5,6,7-位進(jìn)行衍生修飾的多取代靛紅衍生物,并對(duì)其進(jìn)行了體外抑制腫瘤細(xì)胞生長(zhǎng)活性的研究,根據(jù)初步構(gòu)效關(guān)系,又對(duì)1,3,7-位做了進(jìn)一步結(jié)構(gòu)修飾與活性研究。本課題以不同位置的不同取代的苯胺為原料,通過(guò)四條合成路線,經(jīng)Sandmeyer法(成肟、傅克反應(yīng))、溴化、硝化、氧化、酯化、重氮化還原、烷化等一系列反應(yīng)共合成了68個(gè)目標(biāo)化合物,其結(jié)構(gòu)經(jīng)1HNMR、13C NMR和MS進(jìn)行了確證,其中41個(gè)化合物未見(jiàn)文獻(xiàn)報(bào)道。選用人白血病細(xì)胞(K562)、人肝癌細(xì)胞(HepG2)人結(jié)腸癌細(xì)胞(HT-29)對(duì)目標(biāo)化合物進(jìn)行體外腫瘤細(xì)胞生長(zhǎng)抑制活性的研究,結(jié)果表明：當(dāng)多取代靛紅衍生物5-位是吸電子硝基取代,4-位和6-位是較弱的吸電子鹵素取代,7-位是甲酸甲酯或甲酸酰胺,1-位是芐基取代,3-位羰基保持不變時(shí),有助于靛紅衍生物抗腫瘤活性的提高。該課題的研究將為具有抗腫瘤活性的靛紅類(lèi)衍生物新藥研究奠定基礎(chǔ)。
[Abstract]:Indirubin, also known as indomedione or isatin, is an endogenous active substance in mammalian tissues and body fluids.Indirubin and its derivatives have excellent anti-tumor, anti-bacterial, anti-viral and anti-tuberculosis activities.In recent years, more and more attention has been paid to the organic synthesis and pharmacological activity of indirubin derivatives.There are many kinds of chemical reactions on pyrrole ring and benzene ring of indirubin and its derivatives, which provides a wide space for the study of its derivatives.In the past, most of the indirubin derivatives were synthesized on the indirubin ring with one position substituent and the others on the pyrrole ring.There are few studies on the synthesis and bioactivity of indirubin in benzene ring.In this paper, we designed and synthesized a series of polysubstituted indirubin derivatives modified at 4 ~ 5 ~ 6 ~ 6 ~ (-) ~ (-) position of indirubin, and studied their inhibitory activity on tumor cell growth in vitro, according to the preliminary structure-activity relationship.The structure modification and the activity of the 1 ~ 3 ~ 3 ~-~-site were also studied.68 target compounds were synthesized by a series of alkylation reactions. Their structures were confirmed by 1HNMR-13C NMR and MS, among which 41 compounds were not reported in literature.Human leukemia cell line K562and human hepatoma cell line HepG2) were used to study the growth inhibitory activity of the target compounds on tumor cells in vitro.The results show that when the 5-position of the polysubstituted indirubin derivatives is the electron-absorbing nitro-substituted 4-site and the 6-position is the weaker electron-absorbent halogen substitution-7-position is methyl formate or the 1-position of amides formate is benzyl substituted 3-carbonyl, the carbonyl position remains unchangedIt is helpful to enhance the antitumor activity of indirubin derivatives.The research will lay a foundation for the study of new drugs of indirubin derivatives with anti-tumor activity.
【學(xué)位授予單位】：天津科技大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類(lèi)號(hào)】：R914.5;R96

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 李豐橋,岳旺,南勝,張健,劉占濤;吲哚醌對(duì)大鼠杏仁核點(diǎn)燃的抑制作用[J];藥學(xué)學(xué)報(bào);1999年01期

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本文編號(hào)：1709243