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  本文關(guān)鍵詞： 雙核鉑抗腫瘤藥物 trans-1R 2R-環(huán)己二胺 葫蘆[7]脲 甲啶鉑 奈達(dá)鉑 體外抗腫瘤活性 藥物載體　出處：《昆明理工大學(xué)》2017年碩士論文　論文類型：學(xué)位論文

【摘要】：近年來,鉑類抗腫瘤藥物已經(jīng)成為臨床治療腫瘤的一線藥物,它具有獨(dú)特的抗腫瘤機(jī)制、良好的抗腫瘤活性以及廣泛的抗腫瘤譜等優(yōu)勢。但是,鉑類抗腫瘤藥物廣泛存在的毒副作用、耐藥性或交叉耐藥性等問題,嚴(yán)重限制了其臨床應(yīng)用。為了克服鉑類藥物的臨床治療缺陷,開發(fā)高效、低毒的新型鉑類抗腫瘤藥物或引入新型的藥物遞送載體是未來鉑類藥物發(fā)展的重要方向。非經(jīng)典雙核鉑類抗腫瘤藥物具有良好的抗腫瘤活性,其抗腫瘤作用機(jī)制與經(jīng)典單核順鉑類抗腫瘤藥物不同。雙核鉑類抗腫瘤藥物能夠與DNA之間形成多點(diǎn)鍵合及鏈間交聯(lián),對DNA的破壞性更大,使DNA難以自我修復(fù)從而發(fā)揮抗腫瘤作用。在一定程度上規(guī)避了經(jīng)典單核順鉑類抗腫瘤藥物所表現(xiàn)出來的臨床缺陷。葫蘆[n]脲及其衍生化是當(dāng)今超分子化學(xué)的研究熱點(diǎn),其在主客體識別、自組裝的應(yīng)用研究十分廣泛。將葫蘆[n]脲及其衍生物作為藥物遞送載體,能夠提高藥物的水溶性及生物利用度,在一定程度上減少藥物的毒副作用�；谏鲜隹紤],本畢業(yè)論文主要分為以下兩個部分:1、設(shè)計并合成一類新型的非經(jīng)典雙核鉑抗腫瘤配合物,并對其進(jìn)行體外抗腫瘤活性研究。基于奧沙利鉑的手性配體trans-1R.2R-環(huán)己二胺和可以作為嵌入基團(tuán)的平面芳香分子苯環(huán)設(shè)計合成了一種手性四齒二胺化合物HL。以HL為配體,制備了六種目標(biāo)新型手性雙核鉑配合物A1-A6,通過元素分析、紅外(IR)、1H NMR和MS等表征手段確定了其結(jié)構(gòu)。通過水溶性測試及體外抗腫瘤實(shí)驗(yàn),篩選出具有良好體外抗腫瘤活性的雙核鉑配合物A2,具有一定的深入研究價值。2、采用新型超分子化學(xué)主體化合物葫蘆[7]脲,研究鉑類藥物的載藥體系特征及其抗腫瘤活性。利用為葫蘆[7]脲作為主體,奈達(dá)鉑和甲啶鉑為客體藥物制備兩種包合物,通過熒光分析法計算Ks值和包合比;運(yùn)用一維核磁、二維核磁、粉末衍射、掃描電鏡等實(shí)驗(yàn)方法證實(shí)了葫蘆[7]脲與兩種鉑類藥物確定形成包合物,并推斷出可能的包結(jié)模式。
[Abstract]:In recent years, platinum anti-tumor drugs have become the first line of clinical treatment of tumor drugs, it has a unique anti-tumor mechanism, good anti-tumor activity and a wide range of anti-tumor spectrum advantages. Platinum antitumor drugs have many problems, such as side effects, drug resistance or cross resistance, which seriously limit their clinical application. In order to overcome the shortcomings of clinical treatment of platinum drugs, the development of high efficiency. Low toxicity new platinum antitumor drugs or the introduction of new drug delivery vectors are important directions for the development of platinum drugs in the future. Non-classical binuclear platinum antitumor drugs have good antitumor activity. Its antitumor mechanism is different from that of classical mononuclear cisplatin antitumor drugs. Binuclear platinum antitumor drugs can form multi-point bonding and interchain crosslinking with DNA, which is more destructive to DNA. This makes it difficult for DNA to repair itself and play an antitumor role. To some extent, it avoids the clinical defects of classical mononuclear cisplatin antitumor drugs. [Urea and its derivation are the research hotspot of supramolecular chemistry nowadays. The application of urea in host and guest recognition and self assembly is very extensive. [As drug delivery carriers, urea and its derivatives can improve the water solubility and bioavailability of drugs, and reduce the side effects of drugs to a certain extent. This thesis is divided into the following two parts: 1. A novel nonclassical binuclear platinum antitumor complex is designed and synthesized. A chiral tetra was synthesized based on the chiral ligand trans-1R.2R- cyclohexanediamine of oxaliplatin and a planar aromatic molecule benzene ring, which can be used as an intercalation group. The dentate diamine compound HL. with HL as the ligand. Six novel chiral binuclear platinum complexes A1-A6 were prepared by elemental analysis, IR). The structure was confirmed by 1H NMR and MS. The binuclear platinum complex A2 with good antitumor activity in vitro was screened by water solubility test and in vitro antitumor test. It has certain deep research value. 2. The new supramolecular chemical host compound cucurbita is used. [7 Urea, study on the characteristics of platinum drug delivery system and its antitumor activity. [7] Urea as the host, Nedaplatin and methylplatin as the guest drugs to prepare two inclusion complexes, the Ks value and inclusion ratio were calculated by fluorescence analysis. By means of one-dimensional nuclear magnetic field, two-dimensional nuclear magnetic field, powder diffraction, scanning electron microscope and other experimental methods, the gourd has been confirmed. [7] Urea was determined to form inclusion complexes with two platinum drugs, and the possible inclusion patterns were inferred.
【學(xué)位授予單位】：昆明理工大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：O641.4;TQ460.1

【參考文獻(xiàn)】

相關(guān)期刊論文 前1條

1 高傳柱;費(fèi)凡;王天帥;楊波;楊健;廖霞俐;;經(jīng)典順鉑類抗腫瘤藥物耐藥性研究綜述[J];昆明理工大學(xué)學(xué)報(自然科學(xué)版);2013年06期

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本文編號：1483443