双亲性三甲川菁染料的合成及抗结直肠癌活性

doi:10.11944/j.issn.1000-0518.2020.11.200126

摘要/Abstract

摘要： 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¹H NMR、¹³C NMR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570 nm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。

关键词: 多功能化疗药物, 三甲川吲哚菁染料, 双亲性, 光谱性能, 抗肿瘤

Abstract: 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.

Key words: multifunctional chemotherapeutics, trimethine indocyanine, amphipathic, spectral property, antitumor

中图分类号:

O626.2

邱娜, 史霄, 杨艺一, 宋男男, 李佳佳, 葛振英, 张磊. 双亲性三甲川菁染料的合成及抗结直肠癌活性[J]. 应用化学, 2020, 37(11): 1262-1267.

QIU Na, SHI Xiao, YANG Yiyi, SONG Nannan, LI Jiajia, GE Zhenying, ZHANG Lei. Synthesis and Anti-colorectal Cancer Activity of Amphipathic Trimethine Indocyanine Dyes[J]. Chinese Journal of Applied Chemistry, 2020, 37(11): 1262-1267.

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