Synthesis, characterization and in vitro photodynamic antimicrobial activity of basic amino acid–porphyrin conjugates

Abstract

Photodynamic antimicrobial chemotherapy (PACT), as a novel and effective modality for the treatment of infection with the advantage of circumventing multidrug resistance, receives great attention in recent years. The photosensitizer is the crucial element in PACT, and cationic porphyrins have been demonstrated to usually be more efficient than neutral and negatively charged analogues towards bacteria in PACT. In this work, three native basic amino acids, l-lysine, l-histidine and l-arginine, were conjugated with amino porphyrins as cationic auxiliary groups, and 13 target compounds were synthesized. This paper reports their syntheses, structural characterizations, oil-water partition coefficients, singlet oxygen generation yields, photo-stability, as well as their photo inactivation efficacies against methicillin-resistant Staphylococcus aureus (MRSA), Escherichia coli and Pseudomonas aeruginosa in vitro. The preliminary structure-activity relationship was discussed. Compound 4i, with porphyrin bearing four lysine moieties, displays the highest photo inactivation efficacy against the tested bacterial strains at 3.91 μM with a low light dose (6 J/cm(2)), and it is stable in serum and lower cytotoxicity to A929 cells. These basic amino acid-porphyrin conjugates are potential photosensitizers for PACT.