5,15-二芳基卟吩衍生物的合成及光动力活性研究  

Synthesis and photodynamic activities of 5,15-diarylporphin derivatives

作　　者：包艳艳 刘银 江颖 丁雅馨 鲍蕾蕾 G.Lavanya 韩一平[2] 陈志龙[1] BAO Yanyan;LIU Lin;JIANG Ying;DING Yaxin;BAO Leilei;G.Lavanya;HAN Yiping;CHEN Zhilong(Department of Pharmaceutical Science and Technology,College of Chemistry and Biology,Donghua University,Shanghai 201620,China;Shanghai Changhai Hospital,Shanghai 200433,China)

机构地区：[1]东华大学化学与生物学院生物医药研究中心,上海201620 [2]上海长海医院,上海200433

出　　处：《激光杂志》2022年第5期201-206,共6页Laser Journal

基　　金：国家自然科学基金(No.21977016);上海市科委基金(No.18430731600,19411970600,19410711000,20430730900,20490740400,21430730100);Foundation of Dongfang Hepatobiliary Surgery Hospital(No.20WQ011);中国博士后基金(No.2020M681126)。

摘　　要：光敏剂在光动力治疗(PDT)中发挥着重要作用。设计合成了一系列二芳基卟吩衍生物M1、M2和M3,采用1H NMR、13C NMR和MS进行了结构表征,测定了三个化合物的光物理化学性能,并且对其光动力抗人食管癌Eca-109细胞的作用效果进行了评估。结果显示:这些化合物的最长紫外-可见吸收波长在635 nm左右,最佳发射波长位于630 nm~637 nm;M1、M2和M3单线态氧生成速率均高于对照药血卟啉单甲醚(HMME);MTT实验结果表明化合物M1和M3均对Eca-109肿瘤细胞具有显著的光动力抑制活性,且两者相比,M1暗毒性更低,光毒性更高;细胞凋亡检测结果显示M1-PDT组坏死率和凋亡率分别为29.18%和9.46%,可见M1具备光毒作用。综上所述,化合物M1可作为治疗食道癌的潜在光敏新药进行深入研究。Photosensitizers have attracted increasing attention as a critical factor in photodynamic therapy(PDT).In this paper,a series of diarylporphyrin derivatives M1,M2 and M3 were designed and synthesized.Their structures were characterized by1H NMR,13C NMR and MS.Photophysical and chemical properties of three compounds were determined,and their photodynamic effects on the proliferation and apoptosis of Eca-109 cells were evaluated.It showed that the longest UV-vis absorption wavelength of these compounds was around 635 nm,the optimum emission wavelength of these compounds was 630-637 nm.The rates of singlet oxygen generation of M1,M2 and M3 were higher than hematoporphyrin monomethyl ether(HMME).Furthermore,cell viability tests indicated that M1 and M3 possessed the specific photodynamic inhibition effects towards Eca-109 cells,and M3 had higher obvious dark toxicity than M1.The results of apoptosis detection showed that the necrosis rate and apoptosis rate of M1-PDT group were29.18%and 9.46%,respectively,indicating that M1 had phototoxic effect.In conclusion,M1 had excellent photodynamic activities against Eca-109 cells,which could be a potential photosensitive drug for further study.

关 键 词：光敏剂 光动力疗法 二芳基卟吩 肿瘤细胞 

分 类 号：R914.4[医药卫生—药物化学]