Mion Giuliana, Gianferrara Teresa, Bergamo Alberta, Gasser Gilles, Pierroz Vanessa, Rubbiani Riccardo, Vilar Ramon, Leczkowska Anna, Alessio Enzo
Department of Chemical & Pharmaceutical Sciences, Università degli Studi di Trieste, P.le Europa 1, 34127, Trieste, Italy.
Callerio Foundation Onlus, Via A. Fleming 22-31, 34127, Trieste, Italy.
ChemMedChem. 2015 Nov;10(11):1901-14. doi: 10.1002/cmdc.201500288. Epub 2015 Sep 2.
In the search for alternative photosensitizers for use in photodynamic therapy (PDT), herein we describe two new water-soluble porphyrins, a neutral fourfold-symmetric compound and a +3-charged tris-methylpyridinium derivative, in which either four or one [1,4,7]-triazacyclononane (TACN) units are connected to the porphyrin macrocycle through a hydrophilic linker; we also report their corresponding tetracationic Re(I) conjugates. The in vitro (photo)toxic effects of the compounds toward the human cell lines HeLa (cervical cancer), H460M2 (non-small-cell lung carcinoma), and HBL-100 (non-tumorigenic epithelial cells) are reported. Three of the compounds are not cytotoxic in the dark up to 100 μm, and the fourfold-symmetric couple revealed very good phototoxic indexes (PIs). The intracellular localization of all derivatives was studied in HeLa cells by confocal fluorescence microscopy. Although low nuclear localization was observed for some of them, it still prompted us to investigate their capacity to bind both quadruplex and duplex DNA; we observed significant selectivity in the tris-methylpyridinium derivatives for G-quadruplex interactions.
在寻找用于光动力疗法（PDT）的替代光敏剂的过程中，我们在此描述了两种新的水溶性卟啉，一种中性的四重对称化合物和一种带 +3 电荷的三甲基吡啶鎓衍生物，其中四个或一个 [1,4,7] - 三氮杂环壬烷（TACN）单元通过亲水性连接基连接到卟啉大环上；我们还报告了它们相应的四价铼（I）共轭物。报道了这些化合物对人细胞系 HeLa（宫颈癌）、H460M2（非小细胞肺癌）和 HBL - 100（非致瘤性上皮细胞）的体外（光）毒性作用。其中三种化合物在黑暗中浓度高达 100 μM 时无细胞毒性，四重对称的一对显示出非常好的光毒性指数（PIs）。通过共聚焦荧光显微镜研究了所有衍生物在 HeLa 细胞中的细胞内定位。尽管其中一些观察到低核定位，但这仍促使我们研究它们与四重链和双链 DNA 结合的能力；我们观察到三甲基吡啶鎓衍生物对 G - 四重链相互作用具有显著的选择性。
