双亲性三甲川菁染料的合成及抗结直肠癌活性

Synthesis and Anti-colorectal Cancer Activity of Amphipathic Trimethine Indocyanine Dyes

菁染料双亲性的提高有利于自身抗肿瘤活性的提升。探索了三甲川吲哚菁染料(Cy3)转化为多功能小分子化疗药物的可行性。通过向吲哚环“N”上引入聚乙二醇(PEG)醚链,设计合成了两种双亲性三甲川吲哚菁染料:Cy3-DIPEG和Cy3-SO3-DIPEG。二者产率约40%,其结构均经1HNMR、13CNMR和MS表征。光谱测试表明Cy3-DIPEG和Cy3-SO3-DIPEG在水中的最大荧光发射波长在570nm左右,荧光量子产率(Ф)分别为0.06和0.13。采用噻唑蓝(MTT)法测试了两种染料对人结直肠癌细胞株(SW480和HCT-116)的体外抗肿瘤活性,并通过亚细胞器定位实验初探其机制。结果表明,Cy3-DIPEG能穿过肿瘤细胞膜蓄积在线粒体内,显著抑制人结直肠癌细胞增殖,但Cy3-SO3-DIPEG无法进入肿瘤细胞内,无抗肿瘤活性。

The improvement of the amphipathicity of cyanine dyes is conducive to the improvement of its own antitumor activity.In this paper,the feasibility of converting trimethine indocyanine dye(Cy3)into multifunctional small-molecule chemotherapy drug was explored for the first time.Two amphipathic trimethine indocyanine dyes of Cy3-DIPEG and Cy3-SO3-DIPEG containing polyethylene glycol(PEG)chains on the indol“N”were designed and synthesized in yields of about 40%.The structure of the product was identified by 1H NMR and 13C NMR spectroscopy and mass spectroscopy.The maximal fluorescence emission wavelengths of Cy3-DIPEG and Cy3-SO3-DIPEG in water are about 570 nm,and their fluorescence quantum yields(Ф)are 0.06 and 0.13,respectively.The antitumor activities of two dyes on human colorectal cancer cell lines(SW480 and HCT-116)were tested in vitro by the thiazole blue(MTT)assay and the antitumor mechanism was initially explored by subcellular localization experiments.The results show that Cy3-DIPEG can accumulate in mitochondria through the tumor cell membrane,and significantly inhibit the proliferation of human colorectal cancer cells,but Cy3-SO3-DIPEG cannot penetrate into the tumor cell and has no antitumor activity.