發(fā)布時(shí)間：2021-04-05 14:33

　　噻唑環(huán)是一類含有氮硫雜原子的重要五元芳香雜環(huán),具有富電子性,易通過氫鍵、配位鍵、π-π堆積、范德華力、靜電和疏水作用等多種非共價(jià)鍵與生物體內(nèi)的多種酶、蛋白質(zhì)、核酸及其他活性位點(diǎn)發(fā)生作用,表現(xiàn)出多種生物活性,因此噻唑環(huán)被廣泛用于藥物設(shè)計(jì)與開發(fā)。隨著眾多噻唑類化合物成功用于臨床,如抗生素藥物頭孢、抗癌藥物達(dá)沙替尼、消炎藥物美洛昔康、抗寄生蟲藥物硝唑尼特等均作為臨床首選一線藥物,基于噻唑類藥物的研發(fā)幾乎涵蓋了整個(gè)醫(yī)藥領(lǐng)域,并取得了杰出成果。更為重要的是噻唑類化合物在抗細(xì)菌、抗真菌領(lǐng)域發(fā)揮了尤為重要的作用,已有大量研究針對(duì)噻唑類化合物多靶點(diǎn)活性分子的研發(fā),為臨床提供了越來越多的耐受性好、高活性、廣譜、低毒性、生物利用度高、藥代動(dòng)力學(xué)性質(zhì)好的噻唑類化合物作為候選藥物或藥物分子,顯示出了其在醫(yī)藥領(lǐng)域的巨大開發(fā)價(jià)值和潛在的寬廣應(yīng)用前景。基于近年來國(guó)內(nèi)外關(guān)于噻唑類藥物的研究與開發(fā)現(xiàn)狀,以及課題組對(duì)噻唑類化合物抗微生物研究工作的延續(xù),本論文基于以下思想設(shè)計(jì)合成了一系列結(jié)構(gòu)新穎的噻唑類化合物,以期得到具有多靶向性且更好生物活性的新型噻唑類化合物。主要對(duì)其進(jìn)行了體外抗細(xì)菌抗真菌活性評(píng)估及構(gòu)效關(guān)系的研究,并對(duì)... 

【文章來源】：西南大學(xué)重慶市 211工程院校 教育部直屬院校

【文章頁(yè)數(shù)】：415 頁(yè)

【學(xué)位級(jí)別】：博士

【文章目錄】：
中文摘要
ABSTRACT
第一章 噻唑類化合物在醫(yī)藥領(lǐng)域研究新進(jìn)展及論文選題 Chapter 1 Recent Research in Thiazoles as Antimicrobial Agents and Strategy of Thesis
    本章詳細(xì)中文摘要
    1.1 Introduction
    1.2 Thiazole-based antibacterial agents
        1.2.1 Aminothiazoles as antibacterial agents
        1.2.2 Other thiazoles as antibacterial agents
        1.2.3 Benzothiazoles as antibacterial agents
    1.3 Thiazole-based antifungal agents
        1.3.1 Hydrazone-combined thiazoles as antifungal agents
        1.3.2 Amide-derived thiazoles as antifungal agents
        1.3.3 Other thiazoles as antifungal agents
    1.4. Conclusion and outlooks
    1.5 Strategy of this thesis
    References
第二章 新型黃連素類噻唑化合物的設(shè)計(jì)合成及其抗微生物作用研究 Chapter 2 Design, Synthesis and Antimicrobial Evaluation of Berberine Thiazole Derivatives
    本章詳細(xì)中文摘要
    2.1 Introduction
    2.2 Results and discussion
        2.2.1 Chemistry
        2.2.2 Biological activity
        2.2.3 Aqueous solubility
        2.2.4 Cytotoxicity
        2.2.5 Bactericidal kinetics
        2.2.6 Drug resistance development
        2.2.7 Bacterial membrane permeabilization
        2.2.8 Supramolecular docking study
        2.2.9 Preliminary antibacterial mechanism study
        2.2.10 Drug combination use of compound II-9c with norfloxacin
    2.3 Conclusion
    2.4 Experimental protocols
        2.4.1 General methods
        2.4.2 Synthesis
        2.4.3 Antimicrobial assay
        2.4.4 Aqueous solubility assay
        2.4.5 Cytotoxicity assay
        2.4.6 Bactericidal kinetic assay
        2.4.7 Resistance assay
        2.4.8 Bacterial membrane permeabilization assay
        2.4.9 Isolating genomic DNA from drug-resistant A. baumanii strain
        2.4.10 Drug-resistant A. baumanii DNA cleavage assay
        2.4.11 Assay for drug combination use
    References
    APPENDIX Ⅰ
第三章 新型香豆素類噻唑化合物的設(shè)計(jì)合成及其抗微生物活性研究 Chapter 3 Design, Synthesis and Antimicrobial Evaluation of Coumarin Thiazoles
    本章詳細(xì)中文摘要
    3.1 Introduction
    3.2 Results and discussion
        3.2.1 Chemistry
        3.2.2 Biological activity
        3.2.3 Cytotoxicity
        3.2.4 Bactericidal kinetics
        3.2.5 Drug resistance development
        3.2.6 Preliminary antibacterial mechanism study
        3.2.7 Supramolecular docking study
    3.3 Conclusion
    3.4 Experimental protocols
        3.4.1 General methods
        3.4.2 Synthesis
        3.4.3 Antimicrobial assay
        3.4.4 Cytotoxicity assay
        3.4.5 Bactericidal kinetic assay
        3.4.6 Resistance assay
        3.4.7 Isolating genomic DNA from drug-resistant E. faecalis strain
        3.4.8 UV absorption spectra
        3.4.9 Fluorescence emission spectra of compound III-11b
        3.4.10 Drug-resistant E. faecalis DNA cleavage experment
        3.4.11 Bacterial membrane permeabilization assay
    References
    APPENDIX Ⅱ
第四章 新型喹諾酮類噻唑化合物的設(shè)計(jì)合成及其抗微生物活性研究 Chapter 4 Design, Synthesis and Antimicrobial Evaluation of Quinolone Thiazoles
    本章詳細(xì)中文摘要
    4.1 Introduction
    4.2 Results and discussion
        4.2.1 Chemistry
        4.2.2 Biological activity
        4.2.3 Mammalian cytotoxicity
        4.2.4 Bactericidal kinetics
        4.2.5 Drug resistance development
        4.2.6 Bacterial membrane permeabilization
        4.2.7 Supramolecular docking study
        4.2.8 Preliminary antibacterial mechanism study
    4.3 Conclusion
    4.4 Experimental
        4.4.1 General methods
        4.4.2 Synthesis
        4.4.3 Antibacterial and antifungal assays
        4.4.4 Cytotoxicity assay
        4.4.5 Bactericidal kinetic assay
        4.4.6 Resistance assay
        4.4.7 Bacterial membrane permeabilization assay
        4.4.8 Isolating genomic DNA from drug-resistant S. aureus strain
        4.4.9 UV absorption spectra
        4.4.10 Topoisomerase IV Inhibition Assay
    References
    APPENDIX Ⅲ
第五章 新型有機(jī)膦咪唑類化合物的設(shè)計(jì)合成及其抗微生物研究 Chapter 5 Design, Synthesis and Biological Evaluation of Organophosphorus Imidazoles
    本章詳細(xì)中文摘要
    5.1 Introduction
    5.2 Results and discussion
        5.2.1 Chemistry
        5.2.2 Spectral analysis
        5.2.3 Biological activity
        5.2.4 Drug combination study
        5.2.5 Resistance study
        5.2.6 Bactericidal kinetic study
        5.2.7 Bacterial membrane permeabilization study
        5.2.8 Interaction with calf thymus DNA
        5.2.9 Partition coefficient and computational analysis
        5.2.10 Supramolecular interactions of compound V-3f with HSA
    5.3 Conclusion
    5.4 Experimental protocols
        5.4.1 General methods
        5.4.2 Synthesis
        5.4.3 Biological assay
        5.4.4 Drug combination assay
        5.4.5 Resistance assay
        5.4.6 Bactericidal kinetic assay
        5.4.7 Bacterial membrane permeabilization assay
        5.4.8 UV absorption and fluorescence emission spectra
    References
    APPENDIX Ⅳ
結(jié)果與展望（Results and prospects）
基金支持（Financial support）
致謝（Acknowledgments）
作者簡(jiǎn)介（A brief introduction to the author）
成果（Achievements）



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