title: A novel set of symmetric methylene blue derivatives exhibits effective bacteria photokilling - a structure-response study.
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.
authors.affiliation: Department of Dermatology, University Medical Center Regensburg, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Gollmer
authors.forename: Ariane
authors.initials: A
authors.lastname: Felgenträger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Bäumler
authors.forename: Tim
authors.initials: T
authors.lastname: Maisch
authors.forename: Andreas
authors.initials: A
authors.lastname: Späth
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects / Q000528:radiation effects; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008027:Light; D008751:Methylene Blue / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D055668:Photochemical Processes; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D026082:Singlet Oxygen / Q000737:chemistry; D013057:Spectrum Analysis; D013211:Staphylococcus aureus / Q000187:drug effects / Q000528:radiation effects; D055672:Static Electricity
chemical_list: D000890:Anti-Infective Agents; D017319:Photosensitizing Agents; D026082:Singlet Oxygen; D008751:Methylene Blue