title: The impact of cationic substituents in phenalen-1-one photosensitizers on antimicrobial photodynamic efficacy.
abstract: Light-mediated killing of pathogens by cationic photosensitizers (PS) is a promising antimicrobial approach avoiding resistance as being present upon the use of antibiotics. In this study we focused on the impact of the substituents in phenalen-1-one PS. Photodynamic efficacy depending on positively charged moieties including a primary aliphatic, quaternary aliphatic, aromatic ammonium and a guanidinium cation was investigated against Gram-positive and Gram-negative pathogens. Considering the altered steric demand and lipophilicity of these functional groups we deduced a structure-activity relationship. SAGUA was the most potent PS in this series reaching a maximum efficacy of ≥6log10 steps of bacteria killing at a concentration of 10 μM upon irradiation with blue light (20 mW cm(-2)) for 60 s (1.2 J cm(-2)) without exhibiting inherent dark toxicity. Its guanidinium moiety may be able to form strong bidentate and directional hydrogen bonds to carboxylate groups of bacterial surfaces in addition to ionic charge attraction. This may supplement fast and effective antimicrobial activity.
authors.affiliation: Department of Conservative Dentistry and Periodontology, University Medical Center Regensburg, Regensburg, Germany.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tabenski
authors.forename: Fabian
authors.initials: F
authors.lastname: Cieplik
authors.forename: Laura
authors.initials: L
authors.lastname: Tabenski
authors.forename: Johannes
authors.initials: J
authors.lastname: Regensburger
authors.forename: Karl-Anton
authors.initials: KA
authors.lastname: Hiller
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Buchalla
authors.forename: Tim
authors.initials: T
authors.lastname: Maisch
authors.forename: Andreas
authors.initials: A
authors.lastname: Späth
mesh_terms: D000190:Actinomyces / Q000187:drug effects; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002412:Cations / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D013293:Enterococcus faecalis / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D043803:Phenalenes / Q000737:chemistry*; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects; D013295:Streptococcus mutans / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D002412:Cations; D043803:Phenalenes; D017319:Photosensitizing Agents; C038036:phenalen-1-one