Abstract
This study focuses on the structure-response relationship of symmetrically substituted phenothiazinium dyes. Four hydrophilic derivatives with the ability of additional hydrogen bonding (, ) or additional electrostatic interaction (, ) were synthesized, photophysically characterized and compared to the parent compound methylene blue (MB, ) and a lipophilic derivative () without additional coordination sites. Derivative was most effective against Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli reaching a maximum photodynamic efficacy of >5log10 steps (≥99.999%) of bacteria killing in 10 minutes (5 μM, 30 J cm(-2)) without inherent dark toxicity after one single treatment with the incoherent light source PDT1200 (λmax = 660 nm, 50 mW cm(-2)). Interestingly, one derivative with two additional primary positive charges () showed selective killing of Escherichia coli (5 μM, 30 J cm(-2), 4log10 steps inactivation (≥99.99%)) and no antimicrobial effect on Staphylococcus aureus. This might allow the development of a new generation of photosensitizers with higher antimicrobial efficacy and selectivity for future applications.
Highlights
Aim of the present study is to investigate the antibacterial effect of additional positive charges or hydrogen bond acceptors on symmetrically substituted, hydrophilic phenothiazine derivatives (Fig. 1)
A set of symmetric phenothiazinium derivatives modified on both auxochromic positions, 3 and 7, was synthesized
In our study we investigated the phototoxicity of symmetrically substituted phenothiazinium derivatives against S. aureus and E. coli as representatives for Gram-positive and Gram-negative bacteria
Summary
Multiple drug resistance is one of the upcoming threats of our century.1 This means, the disease-causing microorganism is able to resist different antimicrobials, especially antibiotics, and antifungal or antiviral drugs.2 many conventional antibacterial strategies fail and there exists an increasing spread of multi-resistant bacteria.3,4 Besides the development of novel antibiotics, other methods for controlling the spread of pathogenic bacteria have been extensively studied.5–8Phenothiazinium dyes belong to the most prominent class of such PS due to their absorption in the red region of the visible spectrum (ε > 5 × 104 L mol−1 cm−1, λmax ∼ 660 nm), their low dark toxicity and their attachment and penetration abilities.10,11 MB 1 and other phenothiazinium derivatives have shown promising antimicrobial photodynamic efficacy towards bacteria such as Staphylococcus aureus (S. aureus),12 Escherichia coli (E. coli)13,14 and methicillin resistant S. aureus.15 These PS are effective against funguses such as Candida species,16,17 tropical pathogens18 and viruses,19 and are applied in the antimicrobial field.
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