The reported results confirm that the presence of positively charged groups on porphyrin frame is fundamental for PSs antibacterial activity, however our data suggest that a moderate degree of lipophilicity, achievable by the introduction of aromatic hydrocarbon side chains on the pyridyl moieties, may improve PSs efficiency. Furthermore dicationic porphyrin 7 seems to be more efficient than the corresponding tetracationic derivatives thus emphasizing an interesting feature involved in the PSs activity.

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.

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A panel of nitro substituted 5,15-diaryl-porphyrins, featuring nitro groups either on the phenyl rings or on one of the two free meso-positions, was synthesized. In the former category, compounds 5-(3-nitrophenyl)-15-phenylporphyrin, 5,15-di(3-nitrophenyl)porphyrin and 5-(4-nitrophenyl)-15-phenylporphyrin were obtained following standard procedures by reacting dipyrromethane and aromatic aldehydes. In the latter category, porphyrins 10-nitro-5,15-diphenylporphyrin, 10-nitro-5-(3-methoxyphenyl)-15-phenylporphyrin and 10-nitro-5,15-di(3-methoxyphenyl)porphyrin were generated by nitration of 5,15-diarylporphyrins with trifluoroacetic acid/sodium nitrite under particularly mild conditions. The new molecules bearing one or two nitro-groups were tested as photosensitizers during in vitro experiments on a human colon adenocarcinoma cell line (HCT116), and their effects were compared with those induced by temoporfin, porfimer sodium and by some previously published electron-rich diarylporphyrins. The results, expressed as IC50 values obtained by the MTT test following 24 h incubation with the photosensitizers and 2 h irradiation with a 500 W tungsten-halogen lamp, indicate that the presence of an electron withdrawing substituent, on a meso-position, decreases the photodynamic activity of the compound. Conversely, 5-(3-nitrophenyl)-15-phenylporphyrin, a non symmetrically substituted diarylporphyrin bearing both one electron-deficient and one lipophilic moiety, resulted in high phototoxic activity.