Comparison between 5,10,15,20-tetraaryl- and 5,15-diarylporphyrins as photosensitizers: synthesis, photodynamic activity, and quantitative structure-activity relationship modeling.
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.
Banfi
Stefano
S
Department of Structural and Functional Biology, University of Insubria, Via H. Dunant 3, 21100 Varese (VA), Italy. stefano.banfi@uninsubria.it
Caruso
Enrico
E
Buccafurni
Loredana
L
Murano
Roberto
R
Monti
Elena
E
Gariboldi
Marzia
M
Papa
Ester
E
Gramatica
Paola
P
D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011166:Porphyrins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D021281:Quantitative Structure-Activity Relationship
D017319:Photosensitizing Agents; D011166:Porphyrins