Banfi Stefano, Caruso Enrico, Buccafurni Loredana, Murano Roberto, Monti Elena, Gariboldi Marzia, Papa Ester, Gramatica Paola
Department of Structural and Functional Biology, University of Insubria, Via H. Dunant 3, 21100 Varese (VA), Italy.
J Med Chem. 2006 Jun 1;49(11):3293-304. doi: 10.1021/jm050997m.
The synthesis of a panel of seven nonsymmetric 5,10,15,20-tetraarylporphyrins, 13 symmetric and nonsymmetric 5,15-diarylporphyrins, and one 5,15-diarylchlorin is described. In vitro photodynamic activities on HCT116 human colon adenocarcinoma cells were evaluated by standard cytotoxicity assays. A predictive quantitative structure-activity relationship (QSAR) regression model, based on theoretical holistic molecular descriptors, of a series of 34 tetrapyrrolic photosensitizers (PSs), including the 24 compounds synthesized in this work, was developed to describe the relationship between structural features and photodynamic activity. The present study demonstrates that structural features significantly influence the photodynamic activity of tetrapyrrolic derivatives: diaryl compounds were more active with respect to the tetraarylporphyrins, and among the diaryl derivatives, hydroxy-substituted compounds were more effective than the corresponding methoxy-substituted ones. Furthermore, three monoarylporphyrins, isolated as byproducts during diarylporphyrin synthesis, were considered for both photodynamic and QSAR studies; surprisingly they were found to be particularly active photosensitizers.
本文描述了一组七种非对称的5,10,15,20 - 四芳基卟啉、十三种对称和非对称的5,15 - 二芳基卟啉以及一种5,15 - 二芳基二氢卟吩的合成。通过标准细胞毒性试验评估了它们对HCT116人结肠腺癌细胞的体外光动力活性。基于理论整体分子描述符，开发了一个包含34种四吡咯光敏剂（PSs）（包括本研究中合成的24种化合物）的预测性定量构效关系（QSAR）回归模型，以描述结构特征与光动力活性之间的关系。本研究表明，结构特征显著影响四吡咯衍生物的光动力活性：二芳基化合物相对于四芳基卟啉更具活性，并且在二芳基衍生物中，羟基取代的化合物比相应的甲氧基取代的化合物更有效。此外，在二芳基卟啉合成过程中作为副产物分离得到的三种单芳基卟啉也进行了光动力和QSAR研究；令人惊讶的是，它们被发现是特别活跃的光敏剂。
