【摘要】 目的:设计、合成活性氧(ROS)/pH双重响应的β-咔啉类小分子荧光探针H8DP,为肿瘤早期诊断提供新的思路。方法:初始原料L-色氨酸和3,4,5-三甲氧基苯甲醛经过环合、氧化、酰肼化、叠氮重排等多步反应得到H8N,再与对硝基苯基氯甲酸酯反应生成活性酯,最后与4-羟甲基苯硼酸频哪醇酯反应得到目标化合物H8DP。采用紫外和荧光光谱研究H8DP的ROS/pH响应性,并从细胞和动物水平评价其肿瘤选择性荧光成像。结果:H8DP在低p H和高ROS水平下产生显著荧光,并能在Hela细胞和小鼠肿瘤组织中选择性成像,实现对肿瘤组织"开-关"模式荧光成像。结论:构建的H8DP具有ROS/pH双重响应性,能在肿瘤组织中选择性荧光成像,为肿瘤早期诊断提供新的思路。更多还原

【Abstract】 Objective: To provide a new idea for the early diagnosis of tumor, we designed and synthesized a ROS/pH dual-responsive small molecule fluorescent probe H8DP based on β-carboline. Methods: The starting materials L-tryptophan and 3,4,5-trimethoxybenzaldehyde generated H8 N through cyclization, oxidation, hydrazidation and azide rearrangement reactions. Then H8N reacted with p-nitrophenyl chloroformate to generate active ester, and finally reacted with 4-(hydroxymethyl) phenylboronic acid pinacol ester to obtain the target compound H8DP. We used UV and fluorescence spectroscopy to study the pH/ROS responsiveness of H8DP, and evaluated its selective fluorescence imaging at the cellular and animal levels. Results: H8DP produced significant fluorescence at low pH and high ROS levels, and performed selective imaging in Hela cells and mouse tumor tissues to achieve “on-off” fluorescence imaging of tumor tissues. Conclusion:The compound H8DP in this article possesses dual ROS/pH responsiveness and can perform selective fluorescence imaging in tumor tissues, providing new ideas for early tumor diagnosis.更多还原