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Photodynamic inactivation of microorganisms known as antibacterial photodynamic therapy (APDT) is one of the most promising and innovative approaches for the destruction of pathogenic microorganisms. Among the photosensitizers (PSs), compounds based on cationic porphyrins/metalloporphyrins are most successfully used to inactivate microorganisms. Series of meso-substituted cationic pyridylporphyrins and metalloporphyrins with various peripheral groups in the third and fourth positions of the pyrrole ring have been synthesized in Armenia. The aim of this work was to determine and test the most effective cationic porphyrins and metalloporphyrins with high photoactivity against Gram negative and Gram positive microorganisms. It was shown that the synthesized cationic pyridylporphyrins/metalloporphyrins exhibit a high degree of phototoxicity towards both types of bacteria, including the methicillin-resistant S. aureus strain. Zinc complexes of porphyrins are more phototoxic than metal-free porphyrin analogs. The effectiveness of these Zn–metalloporphyrins on bacteria is consistent with the level of singlet oxygen generation. It was found that the high antibacterial activity of the studied cationic porphyrins/metalloporphyrins depends on four factors: the presence in the porphyrin macrocycle of a positive charge (+4), a central metal atom (Zn${}^{2+})$ and hydrophobic peripheral functional groups as well as high values of quantum yields of singlet oxygen. The results indicate that meso-substituted cationic pyridylporphyrins/metalloporphyrins can find wider application in photoinactivation of bacteria than anionic or neutral PSs usually used in APDT.

Three imidazolyl-appended porphyrins were synthesized and characterized by ¹H NMR, elemental analyses, MS and UV-vis spectra. Anticancer activities of porphyrins have been evaluated against cutaneous squamous cell carcinoma (A431 cells) in vitro. The results indicate that the porphyrins have high selective cytotoxicity towards A431 cells in the absence of light and improved phototoxic activity upon exposure to UV light. The yield of singlet oxygen generated by porphyrins were also evaluated by measuring the absorption decay of 1,3-diphenylisobenzofuran (DPBF) in DMF. The phototoxicities of porphyrins against A431 cells were enhanced along with the increase of singlet oxygen.

The antimicrobial activity of new meso-tetrakis(N-methyl-6-quinolinyl)-substituted porphyrins and meso-tetrakis(N-methyl-6-quinolinyl)-substituted chlorins is described. The dark toxicity and photosensitising potentials of free-base (TQP and TQC) and its Sn(IV)-complexes [(TQP)Sn(IV) and (TQC)Sn(IV)] were tested on Gram-positive (Staphylococus aureus), Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria and two species of yeasts (Candida albicans and Rhodotorula bogoriensis). The results described in this paper show that TQP and (TQP)Sn(IV) did not inhibit the growth of S. aureus in the dark, but efficiently photosensitize the inactivation of this Gram-positive bacteria. These porphyrins have no appreciable photosensitizing activity towards Gram-negative bacteria. However, (TQP)Sn(IV) shows high dark toxicity against E. coli and P. aeruginosa. The free-base derivatives demonstrated dark activity only in the case of P. aeruginosa. We suppose that these meso-tetrakis(N-methyl-6-quinolinyl)-substituted porphyrins can bind to the Gram-negative bacteria outer membrane receptors that transported vitamin B₁₂. The meso-substituted chlorins TQC and (TQC)Sn(IV) have shown similar efficiency in the dark- and photoinactivation of S. aureus. They revealed a middle level of dark toxicity towards Gram-negative bacteria. The Sn(IV)-complex of chlorin in comparison with free base and metalloporphyrins are more effective in photoinactivation of Gram-negative bacteria. Yeasts, such as Candida albicans and Rhodotorula bogoriensis are more sensitive to photodynamic inactivation as bacterial cells. The effects of (TQP)Sn(IV) and (TQC)Sn(IV) are more expressed than effects of free bases.

Photodynamic therapy (PDT) is approved for clinical indications including several (pre-) cancers of the skin and solid tumors of the brain and the gastrointestinal tract. It operates by an acute cellular response caused by oxidation of cell components following light-induced and photosensitizer-mediated generation of reactive oxygen species. By this, PDT is capable of inducing the major types of cytotoxic responses: autophagy, apoptosis, and necrosis. As excited photosensitizer molecules react rather non-specifically with neighboring molecules, we suggest that with PDT and most (if not any) cell-localizing photosensitizers, all kinds of cellular responses can be provoked — following a strict dose-dependency, i.e. a transition from survival, over apoptosis to necrosis depending on the applied photosensitizer concentration or light dose. In this review, we briefly discuss (i) the types of cell death induced by PDT focusing on apoptosis induction, (ii) a simple experimental approach to quickly assess the dose-dependent phototoxic responses based on viability assays, and (iii) an overview of in vitro apoptosis detection methods for further in depth analyses. With this conceptual framework, we attempt to provide a rational experimental approach for initial in vitro, cell-based characterization of newly synthesized photosensitizers or formulations thereof — thus to plug the gap between subsequent in vivo evaluation and the preceding fundamental (physico-)chemical work devoted to the improvement of photosensitizing drugs based on mainly porphyrins, phthalocyanines and their derivatives.

One novel porphyrin 5,10,15-tris(phenyl)-20-[4-(2-(2-methyl-5-nitro-imidazolyl)ethoxyl)phenyl] porphyrin and its zinc(II) metalloporphyrin were synthesized and characterized by IR, UV-vis, ¹H NMR, MS and elemental analysis. The single crystal structure of zinc(II) porphyrin shows that the Zn(II) ion is coordinated with four nitrogen atoms of porphyrin ring and one oxygen atom of ethanol from axial, forming a five-coordinated square pyramidal geometry. Their cytotoxicity and photodynamic activity against breast cancer cells were studied. The results indicate that both of the porphyrins display high phototoxicity to the breast cancer cells with the negligible dark toxicity. In addition, the photodynamic activity of zinc(II) porphyrin was obviously higher than that of the free porphyrin.