Milanesio M Elisa, Alvarez M Gabriela, Silber Juan J, Rivarola Viviana, Durantini Edgardo N
Departamento de Química, Universidad Nacional de Río Cuarto, Agencia Postal Nro 3, 5800 Río Cuarto, Córdoba, Argentina.
Photochem Photobiol Sci. 2003 Sep;2(9):926-33. doi: 10.1039/b212890j.
A novel 5-[4-(trimethylammonium)phenyl]-10,15,20-tris(2,4,6-trimethoxyphenyl)porphyrin iodide (2) has been synthesized. A positive charge was incorporated at a peripheral position to increase the amphiphilic character of the structure. The photodynamic effect of the cationic porphyrin 2 was compared with that of non-charged 5-(4-aminophenyl)-10,15,20-tris(2,4,6-trimethoxyphenyl)porphyrin (1), both in a homogeneous medium bearing photooxidizable substrates and in vitro on the Hep-2 human larynx carcinoma cell line. Absorption and fluorescence spectroscopic studies in different media show that 2 is essentially unaggregated in solution, and also in human cells. The singlet molecular oxygen, O2(1delta(g)), production was evaluated using 9,10-dimethylanthracene in N,N-dimethylformamide, yielding phi(delta) values of approximately 0.66 for both porphyrins. The addition of beta-carotene suppresses the O2(1delta(g))-mediated photooxidation. L-Tryptophan and guanosine 5'-monophosphate were used as biological substrate models. Porphyrin 2 sensitizes the decomposition of both compounds faster than does 1. In the biological medium, no dark cytotoxicity was observed, even though a high porphyrin concentration (10 microM) and a long incubation time (24 h) were employed. Cell treatments were performed with 5 microM of porphyrin for 24 h. Under these conditions, the uptake of porphyrin 2 into Hep-2 was about 3 times higher than that of 1. Cell survival after irradiation with visible light was dependent upon both the light exposure level and intracellular sensitizer concentration. Thus, a higher photocytotoxic effect was found for porphyrin 2 in comparison to 1. These results show that the amphiphilic monocationic porphyrin 2 could be a promising model for phototherapeutic agents with potential applications in tumor cell inactivation by photodynamic therapy.
一种新型的5-[4-(三甲基铵基)苯基]-10,15,20-三(2,4,6-三甲氧基苯基)碘化卟啉(2)已被合成。在其外围位置引入了一个正电荷以增强该结构的两亲性。将阳离子卟啉2的光动力效应与不带电荷的5-(4-氨基苯基)-10,15,20-三(2,4,6-三甲氧基苯基)卟啉(1)进行了比较，比较分别在含有可光氧化底物的均相介质中和体外对Hep-2人喉癌细胞系进行。在不同介质中的吸收和荧光光谱研究表明，2在溶液中以及在人细胞中基本上不聚集。使用9,10-二甲基蒽在N,N-二甲基甲酰胺中评估单线态分子氧O₂(¹Δg)的产生，两种卟啉的φ(Δ)值均约为0.66。添加β-胡萝卜素可抑制O₂(¹Δg)介导的光氧化。L-色氨酸和5'-单磷酸鸟苷用作生物底物模型。卟啉2比1更快地敏化这两种化合物的分解。在生物介质中，即使使用高卟啉浓度(10 μM)和长孵育时间(24 h)，也未观察到暗细胞毒性。用5 μM卟啉进行细胞处理24 h。在这些条件下，卟啉2进入Hep-2细胞的摄取量比1高约3倍。可见光照射后的细胞存活率取决于光照水平和细胞内敏化剂浓度。因此，与1相比，卟啉2具有更高的光细胞毒性作用。这些结果表明，两亲性单阳离子卟啉2可能是一种有前景的光治疗剂模型，在光动力疗法使肿瘤细胞失活方面具有潜在应用。
