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Background: Photodynamic therapy exploits visible light and photosensitizers to inactivate cells and this methodology is currently used for the treatment of several types of malignancy. Although various tumours are successfully treated with PSs and light, the application on microorganisms (photodynamic antimicrobial chemotherapy) has not yet found specific medical applications and still remains an open field of fundamental research., Purpose: The assessment of the effect of a panel of seven tetraaryl-porphyrins, two commercial (PS 1 and 2) and five synthetic (PS 3-7) in in vitro experiments against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus., Methods: Three of the new photosensitizers (PS 3, 4 and 5) are tetracationic porphyrins and were prepared by N-alkylation of 5,10,15,20-tetra-4-pyridylporphyrin with a large excess of different benzyl chlorides; compound 7 is a dicationic porphyrin and was obtained in a similar way using a lower excess of 4-methoxybenzyl chloride. The neutral porphyrin (PS 6) was previously described. Dose-response curves were obtained titrating the survivors of cell suspensions (10(8)cfu/ml) exposed to the PSs and irradiated with visible light (total fluence rate 266 J/cm2)., Results: The non ionic porphyrin 6 was the least active PS against all the tested bacteria. Cationic PSs 3, 4, 5 and 7 were more active than the commercial 1 and 2. The Gram positive S. aureus was more sensitive to all the PSs than the Gram negative E. coli and P. aeruginosa, the latter being the more resistant one. Compound 7 was found particularly efficient against P. aeruginosa, causing a 7 log units reduction of survivors at a concentration of 8 microM., Conclusions: 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.