【作者】 王鑫； 蒋涛； 刘俊维； 陈长坡； 仉华；

【Author】 Xin Wang;Tao Jiang;Junwei Liu;Hua Zhang;Changpo Chen;School of Chemistry and Chemical Engineering,Henan Normal University;

【机构】 河南师范大学化学化工学院；

【摘要】 药物发现过程包括许多阶段,由于当前药物的研发成本居高不下,故此,新药研发迫切需要新技术、新理论。点击化学(Click chemistry),是通过小单元的拼接,来快速可靠地完成形形色色分子的化学合成。尤其强调开辟以碳-杂原子键(C-X-C)合成为基础的组合化学新方法,并借助这些反应(点击反应)来简单高效地获得分子多样性。点击化学的概念对化学合成领域有很大的贡献,在药物开发和生物医用材料等的诸多领域中,它已经成为目前最为有用和吸引人的合成理念之一[1]。本工作基于对药物在细胞内可视需求,以萘的衍生物苊醌为荧光母体,构筑强荧光类染料(FL-ATP),运用click反应的机理,构建可对药物专一性识别的荧光染料[2]。拟实现其对细胞内药物传递和运输过程中的识别与监控,并将其应用于药物细胞内视踪及药效评价中。在本工作中,对染料分子进行了基本光谱测定,明确了染料分子可与特定药物发生click反应,形成新的染料体系,借此实现细胞内视踪及药效评价。更多还原

【Abstract】 The drug discovery process includes many stages. Due to the high research and development costs of current drugs, new drug research and development urgently require new technologies and new theories. Click chemistry enables fast and reliable chemical synthesis of various colored molecules through the splicing of small molecular units. Particular emphasis has been placed on opening up new combinatorial chemistry based on the synthesis of carbon-heteroatom bonds(C-X-C) and using these reactions(click reactions) to obtain molecular diversity simply and efficiently. The concept of click chemistry has made a great contribution to the field of chemical synthesis. In many fields such as drug development and biomedical materials, it has become one of the most useful and attractive synthetic concepts. This work is based on the visual requirements of drugs in vivo, and uses naphthalene derivatives as fluorescent precursors to construct strong fluorescence dyes(FL-ATP). Using click reaction mechanism, we developed a fluorescence post-labeling system that can be used to specifically recognize drug Erlotinib. It is intended to identify and monitor the intracellular delivery and transportation of Erlotinib, and to evaluate its efficacy in living cells. The basic spectrometry results have clarified that the post-labeling system could click react with Erlotinib to form a new dye system, and achieve intracellular visualization and efficacy evaluation.更多还原