Antibacterial Activity of Synthetic Cationic Iron Porphyrins

Abstract

Widespread antibiotic resistance demands new strategies for fighting infections. Porphyrin-based compounds were long ago introduced as photosensitizers for photodynamic therapy, but light-independent antimicrobial activity of such compounds has not been systematically explored. The results of this study demonstrate that synthetic cationic amphiphilic iron N-alkylpyridylporphyrins exert strong bactericidal action at concentrations as low as 5 μM. Iron porphyrin, FeTnHex-2-PyP, which is well tolerated by laboratory animals, efficiently killed Gram-negative and Gram-positive microorganisms. Its bactericidal activity was oxygen-independent and was controlled by the lipophilicity and accumulation of the compound in bacterial cells. Such behavior is in contrast with the anionic gallium protoporphyrin IX, whose efficacy depends on cellular heme uptake systems. Under aerobic conditions, however, the activity of FeTnHex-2-PyP was limited by its destruction due to redox-cycling. Neither iron released from the Fe-porphyrin nor other decomposition products were the cause of the bactericidal activity. FeTnHex-2-PyP was as efficient against antibiotic-sensitive E. coli and S. aureus as against their antibiotic-resistant counterparts. Our data demonstrate that development of amphiphilic, positively charged metalloporphyrins might be a promising approach in the introduction of new weapons against antibiotic-resistant strains.

The Cytochemical Study of Oxygen-Dependent and Oxygen-Independent Components of Bactericidal Activity of Dog' Peripheral Blood Leukocytes

“…The study results correspond to the well-known fact that a certain number of peripheral blood granulocytes contains substances responsible for oxygen-dependent (Smirnova et al 2018) (spontaneous NBT test (Fig. 1-1) and oxygen-independent (Tovmasyan et al 2020) (cationic proteins (Fig. 1-3) bactericidal activity (Tohyama et al 2019).…”

Latest trends on photodynamic disinfection of Gram-negative bacteria: photosensitizer’s structure and delivery systems

“…6) were compared, testing the influence of the alkyl's length chain on E. coli disinfection, where it was found that the compound 20, bearing an alkyl chain with eight carbons, decreased the bacterial viability in around 97%, while compound 17 was only able to reduce bacterial viability by 20% [43,44] . These results were compared with similar iron(III)-metalated porphyrins [45] , obtaining similar results and bearing the same conclusions: for Gramnegative inactivation not only charges are needed but also lipophilicity is desirable. Then, we could hypothesize that the cationic charges ensure a tight interaction with the negatively charged LPS, while the lipophilicity ensures the penetration through the two cellular membranes; then, a highly cationized molecule could be bound tightly to the outside of the cell, preventing its internalization and preventing its photodynamic effect, as ROS are unable to diffuse through the bacterial envelope.…”

“…As photodynamic applications against microorganisms gain popularity, researchers are likely to seek for alternatives away from already established research lines, diversifying the photodynamic systems used.PS We have previously addressed several metals, such as iron [45] , iridium [60], palladium [39] , ruthenium [54] , and lutetium [52] , are used to form complexes with PSs. However, the use of metals is not limited to the decoration of already established PSs, and in the following sections we will present several examples where metallic complexes permit the formation of efficient photosensitizing systems.…”

The Comparison of Advanced Electrospun Materials Based on Poly(-3-hydroxybutyrate) with Natural and Synthetic Additives

“…The magnetic properties of Fe(TPP)Cl are good enough for biomedical and therapeutic application [ 54 ]. It is antimicrobial active against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli [ 55 ]. Fe(TPP)Cl has low toxicity to eukaryotic cells [ 13 ].…”