研究背景:AMPK是細(xì)胞重要的能量感受器,控制細(xì)胞能量代謝以及分解代謝路徑。近年來(lái),AMPK已經(jīng)成為腫瘤預(yù)防和治療的靶點(diǎn)之一,激活A(yù)MPK蛋白能抑制腫瘤細(xì)胞增殖。本課題主要分兩部分進(jìn)行:1、氯胍抗腫瘤作用和機(jī)制;2、苯乙雙胍衍生物類(lèi)AMPK激活劑構(gòu)效關(guān)系定量分析。研究方法:本課題選用UMUC3、T24和A549三種癌細(xì)胞系。MTT實(shí)驗(yàn)檢測(cè)細(xì)胞增殖、克隆形成實(shí)驗(yàn)和劃痕實(shí)驗(yàn)分別用于檢測(cè)氯胍對(duì)癌細(xì)胞集落形成和遷移的影響。Western blot實(shí)驗(yàn)檢測(cè)氯胍對(duì)AMPK信號(hào)通路的影響。利用文獻(xiàn)獲得54種苯乙雙胍類(lèi)似物的IC50值并建立2D模型�；衔锓殖�2組,其中40個(gè)化合物用于建模,余下的14個(gè)化合物用于對(duì)已建模型的測(cè)試。利用40個(gè)化合物進(jìn)行結(jié)構(gòu)定量分析并建立2D模型,利用該模型對(duì)余下的14個(gè)化合物進(jìn)行分子對(duì)接以及分子描述,結(jié)果表明所有化合物都符合Lipinski五規(guī)則。實(shí)驗(yàn)結(jié)果:氯胍對(duì)呈劑量依賴性抑制3種癌細(xì)胞系增殖、克隆形成以及遷移。Western blot結(jié)果表明氯狐激活A(yù)MPK信號(hào)通路。所有建模組化合物滿足Lipinski五規(guī)則,由40個(gè)建模化合物的回歸分析得到的線性相關(guān)圖顯示出良好的...

【文章頁(yè)數(shù)】：72 頁(yè)

【學(xué)位級(jí)別】：碩士

【文章目錄】：
ABSTRACT
中文摘要
CHAPTER 1 INTRODUCTION
CHAPTER 2 MATERIALS AND METHODS
    2.1 EXPERIMENTAL MATERIALS
        2.1.1 REAGENTS AND KITS
        2.1.2 MAIN CONSUMABLES
        2.1.3 EXPERIMENTAL EQUIPMENT
        2.1.4 MAIN COMPUTER SOFTWARES
        2.1.5 CELL LINES
    2.2 CELL EXPERIMENT METHOD
        2.2.1 Preparation of reagents for cell culture
        2.2.2 Cell Recovery
        2.2.3 Cell Culture and Subculture
        2.2.4 Cell freezing
        2.2.5 Cell Count
        2.2.6 MTT assay for cell proliferation
        2.2.7 Cell Cloning Experiment
        2.2.8 Protein Expression Detection
    2.3 QSAR of Phenformin Derivatives
        2.3.1 Data Collection and Molecule Preparation
        2.3.2 QSAR study
        2.3.3 ADME Study
        2.3.4 Molecular Docking
CHAPTER 3 RESULTS
    3.1 Proguanil inhibits bladder cancer cell lines proliferation better than Metformin andPhenformin
    3.2 Proguanil suppresses colony formation
    3.3 Proguanil inhibits the migration of cells
    3.4 Proguanil modulates anti-proliferative effect through the AMPK pathway
    3.5 QSAR Study
    3.6 ADME STUDY
    3.7 MOLECULAR DOCKING
CHAPTER 4 DISCUSSION
CHAPTER 5 CONCLUSION
REFERENCES
PAPERS PUBLISHED DURING MY STUDY
ACKNOWLEDGEMENT



本文編號(hào)：3901819