稀土—全反式維甲酸—氨基酸三元配合物的合成、表征及抗腫瘤活性研究
發(fā)布時(shí)間：2018-09-10 21:38
【摘要】：癌癥一直嚴(yán)重威脅著人們的健康，也是全球疾病治療方面的主要負(fù)擔(dān)。人類與腫瘤疾病的對(duì)抗史可以追溯到2000年前，近50年來，隨著醫(yī)學(xué)研究的進(jìn)步，人們對(duì)腫瘤的認(rèn)識(shí)有了根本的改變，，對(duì)腫瘤的防治成為各界人士關(guān)注的焦點(diǎn)。對(duì)于無機(jī)藥物研究者，一個(gè)重要的挑戰(zhàn)是怎樣較好的平衡金屬配合物的藥理活性和潛在的毒性，進(jìn)而實(shí)現(xiàn)對(duì)金屬配合物的合理設(shè)計(jì)。 為進(jìn)一步研究稀土配合物作為藥物使用方面的應(yīng)用，本論文報(bào)道了稀土離子(Nd3+、Eu3+、La3+、Sc3+)-全反式維甲酸-氨基酸(L-精氨酸、L-纈氨酸、L-谷氨酸)三元配合物的合成、表征和其抗腫瘤活性進(jìn)行體外實(shí)驗(yàn)的研究結(jié)果。結(jié)果表明，配合物的抗腫瘤活性基本強(qiáng)于配體全反式維甲酸、三種相應(yīng)的氨基酸和金屬硝酸鹽，稀土配合物對(duì)三種癌細(xì)胞株(HepG2A549Hela)生長的抑制作用基本上隨配合物濃度的增大而增強(qiáng)。通過熒光,黏度法等研究了配合物與藥物靶分子DNA的相互作用，結(jié)果表明配合物與DNA以嵌入的方式相互作用，推測(cè)配合物抗腫瘤活性的起效與這種嵌入DNA雙螺旋結(jié)構(gòu)的作用方式有關(guān)。本論文的研究工作為設(shè)計(jì)合成高效低毒的稀土抗腫瘤藥物提供了一定的思路和實(shí)驗(yàn)依據(jù)。 本論文分為以下五部分： 1.綜述了抗腫瘤藥物的研究進(jìn)展。重點(diǎn)敘述了金屬及其配合物、維甲酸、氨基酸和稀土元素的結(jié)構(gòu)特點(diǎn)、性質(zhì)、生理活性及其在抗腫瘤方面的研究現(xiàn)狀；介紹了金屬與DNA相互作用的模式，抗腫瘤藥物篩選常用的方法。 2.合成了稀土離子(Nd3+、Eu3+、La3+、Sc3+)-全反式維甲酸-L-精氨酸鹽酸鹽四種新型的三元配合物，利用元素分析、紅外光譜、熱重分析和紫外光譜對(duì)配合物進(jìn)行了表征，并利用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴鹽(MTT)測(cè)試方法，初步探討了配合物對(duì)體外培養(yǎng)的人肝癌細(xì)胞HepG2、人肺癌細(xì)胞A549和人宮頸癌細(xì)胞Hela生長的影響。采取光譜和黏度法探究了配合物與ct-DNA的作用模式。實(shí)驗(yàn)結(jié)果表明，ScL2L'Cl配合物有較大的潛在藥物使用價(jià)值。 3.合成了稀土離子(Nd3+、Eu3+、La3+、Sc3+)-全反式維甲酸-L-纈氨酸四種新型的三元配合物，利用元素分析、紅外光譜、熱重分析和紫外光譜對(duì)配合物進(jìn)行了表征，并利用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴鹽(MTT)測(cè)試方法，初步探討了配合物對(duì)體外培養(yǎng)的人肝癌細(xì)胞HepG2、人肺癌細(xì)胞A549和人宮頸癌細(xì)胞Hela生長的影響。采取光譜和黏度法探究了配合物與ct-DNA的作用模式。實(shí)驗(yàn)結(jié)果表明，EuL2L'和ScL2L'配合物在抗腫瘤藥物的研發(fā)上有較好的研究前景。 4.合成了稀土離子(Nd3+、Eu3+、La3+、Sc3+)-全反式維甲酸-L-谷氨酸四種新型的三元配合物，利用元素分析、紅外光譜、熱重分析和紫外光譜對(duì)配合物進(jìn)行了表征，并利用3-(4,5-二甲基噻唑-2)-2,5-二苯基四氮唑溴鹽(MTT)測(cè)試方法，初步探討了配合物對(duì)體外培養(yǎng)的人肝癌細(xì)胞HepG2、人肺癌細(xì)胞A549和人宮頸癌細(xì)胞Hela生長的影響。采取光譜和黏度法探究了配合物與ct-DNA的作用模式。實(shí)驗(yàn)結(jié)果表明，EuL2L'是一種潛在的抗癌藥物，需要做更深入的研究來確定它的藥用價(jià)值。 5.報(bào)道了四種稀土氧化物(Nd2O3、Eu2O3、La2O3、Sc2O3)對(duì)人肝癌細(xì)胞HepG2的抗腫瘤活性進(jìn)行體外實(shí)驗(yàn)的研究結(jié)果，進(jìn)一步從稀土離子的角度總結(jié)了稀土三元配合物對(duì)人肝癌細(xì)胞HepG2、人肺癌細(xì)胞A549和人宮頸癌細(xì)胞Hela三株腫瘤細(xì)胞增殖的抑制作用的變化趨勢(shì)，以期在抗腫瘤藥物研究方面提供一定的實(shí)驗(yàn)依據(jù)。
[Abstract]:Cancer has been a serious threat to people's health and a major burden on the treatment of diseases worldwide. The history of the fight against cancer can be traced back to 2000 years ago. In the past 50 years, with the progress of medical research, people's understanding of cancer has changed fundamentally. The prevention and treatment of cancer has become the focus of attention of people from all walks of life. An important challenge for drug researchers is how to balance the pharmacological activity and potential toxicity of metal complexes to achieve a rational design of metal complexes.
In order to further study the application of rare earth complexes as drugs, the synthesis, characterization and antitumor activity of ternary complexes of rare earth ions (Nd3 +, Eu3 +, La3 +, Sc3 +) - all-trans retinoic acid-amino acid (L-arginine, L-valine, L-glutamic acid) were studied in vitro. The inhibitory effect of three amino acids, metal nitrates and rare earth complexes on the growth of three cancer cell lines (HepG2? A549? Hela) was enhanced with the increase of the concentration of the complexes. The interaction between the complexes and the target DNA was studied by fluorescence and viscosity methods. It is suggested that the interaction between the complexes and DNA is in the way of embedding, and the anticancer activity of the complexes may be related to the double helix structure of DNA.
This thesis is divided into five parts:
1. The research progress of antitumor drugs is reviewed. The structural characteristics, properties, physiological activities and antitumor research status of metals and their complexes, retinoic acid, amino acids and rare earth elements are described in detail.
2. Four new ternary complexes of rare earth ions (Nd3 +, Eu3 +, La3 +, Sc3 +) with all-trans retinoic acid-L-arginine hydrochloride were synthesized. The complexes were characterized by elemental analysis, infrared spectroscopy, thermogravimetric analysis and ultraviolet spectroscopy, and were tested by 3-(4,5-dimethylthiazole-2) -2,5-diphenyltetrazolium bromide (MTT). The effect of the complex on the growth of human hepatoma cell HepG2, human lung cancer cell A549 and human cervical cancer cell Hela in vitro was studied by spectroscopy and viscosity method.
3. Four new ternary complexes of rare earth ions (Nd3 +, Eu3 +, La3 +, Sc3 +) - all-trans retinoic acid-L-valine were synthesized. The complexes were characterized by elemental analysis, infrared spectroscopy, thermogravimetric analysis and ultraviolet spectroscopy. The complexes were characterized by 3-(4,5-dimethylthiazole-2) -2,5-diphenyltetrazolium bromide (MTT) method. The effects of EuL2L'and SCL2L' complexes on the growth of human hepatoma cell HepG2, human lung cancer cell A549 and human cervical cancer cell Hela were studied by spectroscopy and viscosity method.
4. Four new ternary complexes of rare earth ions (Nd3 +, Eu3 +, La3 +, Sc3 +) - all-trans retinoic acid-L-glutamic acid were synthesized. The complexes were characterized by elemental analysis, infrared spectroscopy, thermogravimetric analysis and ultraviolet spectroscopy. The complexes were characterized by 3-(4,5-dimethylthiazole-2) -2,5-diphenyltetrazolium bromide (MTT) method. The effects of EuL2L'on the growth of human hepatoma cell HepG2, human lung cancer cell A549 and human cervical cancer cell Hela were studied by spectroscopy and viscosity method.
5. The antitumor activity of four rare earth oxides (Nd2O3, Eu2O3, La2O3, Sc2O3) on human hepatoma cell line HepG2 in vitro was studied. The inhibitory effects of rare earth ternary complexes on the proliferation of human hepatoma cell HepG2, human lung cancer cell A549 and human cervical cancer cell Hela were summarized from the perspective of rare earth ions. In order to provide some experimental evidence for the research of antineoplastic agents.
【學(xué)位授予單位】：西北師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R914.3;O627.3
本文編號(hào)：2235686
[Abstract]:Cancer has been a serious threat to people's health and a major burden on the treatment of diseases worldwide. The history of the fight against cancer can be traced back to 2000 years ago. In the past 50 years, with the progress of medical research, people's understanding of cancer has changed fundamentally. The prevention and treatment of cancer has become the focus of attention of people from all walks of life. An important challenge for drug researchers is how to balance the pharmacological activity and potential toxicity of metal complexes to achieve a rational design of metal complexes.
In order to further study the application of rare earth complexes as drugs, the synthesis, characterization and antitumor activity of ternary complexes of rare earth ions (Nd3 +, Eu3 +, La3 +, Sc3 +) - all-trans retinoic acid-amino acid (L-arginine, L-valine, L-glutamic acid) were studied in vitro. The inhibitory effect of three amino acids, metal nitrates and rare earth complexes on the growth of three cancer cell lines (HepG2? A549? Hela) was enhanced with the increase of the concentration of the complexes. The interaction between the complexes and the target DNA was studied by fluorescence and viscosity methods. It is suggested that the interaction between the complexes and DNA is in the way of embedding, and the anticancer activity of the complexes may be related to the double helix structure of DNA.
This thesis is divided into five parts:
1. The research progress of antitumor drugs is reviewed. The structural characteristics, properties, physiological activities and antitumor research status of metals and their complexes, retinoic acid, amino acids and rare earth elements are described in detail.
2. Four new ternary complexes of rare earth ions (Nd3 +, Eu3 +, La3 +, Sc3 +) with all-trans retinoic acid-L-arginine hydrochloride were synthesized. The complexes were characterized by elemental analysis, infrared spectroscopy, thermogravimetric analysis and ultraviolet spectroscopy, and were tested by 3-(4,5-dimethylthiazole-2) -2,5-diphenyltetrazolium bromide (MTT). The effect of the complex on the growth of human hepatoma cell HepG2, human lung cancer cell A549 and human cervical cancer cell Hela in vitro was studied by spectroscopy and viscosity method.
3. Four new ternary complexes of rare earth ions (Nd3 +, Eu3 +, La3 +, Sc3 +) - all-trans retinoic acid-L-valine were synthesized. The complexes were characterized by elemental analysis, infrared spectroscopy, thermogravimetric analysis and ultraviolet spectroscopy. The complexes were characterized by 3-(4,5-dimethylthiazole-2) -2,5-diphenyltetrazolium bromide (MTT) method. The effects of EuL2L'and SCL2L' complexes on the growth of human hepatoma cell HepG2, human lung cancer cell A549 and human cervical cancer cell Hela were studied by spectroscopy and viscosity method.
4. Four new ternary complexes of rare earth ions (Nd3 +, Eu3 +, La3 +, Sc3 +) - all-trans retinoic acid-L-glutamic acid were synthesized. The complexes were characterized by elemental analysis, infrared spectroscopy, thermogravimetric analysis and ultraviolet spectroscopy. The complexes were characterized by 3-(4,5-dimethylthiazole-2) -2,5-diphenyltetrazolium bromide (MTT) method. The effects of EuL2L'on the growth of human hepatoma cell HepG2, human lung cancer cell A549 and human cervical cancer cell Hela were studied by spectroscopy and viscosity method.
5. The antitumor activity of four rare earth oxides (Nd2O3, Eu2O3, La2O3, Sc2O3) on human hepatoma cell line HepG2 in vitro was studied. The inhibitory effects of rare earth ternary complexes on the proliferation of human hepatoma cell HepG2, human lung cancer cell A549 and human cervical cancer cell Hela were summarized from the perspective of rare earth ions. In order to provide some experimental evidence for the research of antineoplastic agents.
【學(xué)位授予單位】：西北師范大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2014
【分類號(hào)】：R914.3;O627.3
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