title: Antimicrobial photodynamic efficacy of side-chain functionalized benzo[a]phenothiazinium dyes.
abstract: 5-(Ethylamino)-9-diethylaminobenzo[a]phenothiazinium chloride (EtNBS) is a photosensitizer (PS) with broad antimicrobial photodynamic activity. The objective of this study was to determine the antimicrobial photodynamic effect of side chain/end group modifications of EtNBS on two representative bacterial Gram-type-specific strains. Two EtNBS derivatives were synthesized, each functionalized with a different side-chain end-group, alcohol or carboxylic acid. In solution, both exhibited photochemical properties consistent with those of the EtNBS parent molecule. In vitro photodynamic therapy experiments revealed an initial Gram-type-specificity with two representative strains; both derivatives were phototoxic to Staphylococcus aureus 29,213 but the carboxylic acid derivative was nontoxic to Escherichia coli 25,922. This difference in photodynamic efficacy was not due to a difference in the binding of the two molecules to the bacteria as the amount of both derivatives bound by bacteria was identical. Interestingly, the carboxylic acid derivative produced no fluorescence emission when observed in cultures of E. coli via fluorescence microscopy. These early findings suggest that the addition of small functional groups could achieve Gram-type-specific phototoxicity through altering the photodynamic activity of PSs and deserve further exploration in a larger number of representative strains of each Gram type.
authors.affiliation: Wellman Center for Photomedicine, Massachusetts General Hospital and Department of Dermatology, Harvard Medical School, Boston, MA, USA.
authors.forename: Sarika
authors.initials: S
authors.lastname: Verma
authors.forename: Ulysses W
authors.initials: UW
authors.lastname: Sallum
authors.forename: Humra
authors.initials: H
authors.lastname: Athar
authors.forename: Lauren
authors.initials: L
authors.lastname: Rosenblum
authors.forename: James W
authors.initials: JW
authors.lastname: Foley
authors.forename: Tayyaba
authors.initials: T
authors.lastname: Hasan
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000633:toxicity; D004926:Escherichia coli / Q000187:drug effects / Q000528:radiation effects; D015394:Molecular Structure; D010640:Phenothiazines / Q000737:chemistry* / Q000633:toxicity; D017319:Photosensitizing Agents / Q000737:chemistry* / Q000633:toxicity; D013211:Staphylococcus aureus / Q000187:drug effects / Q000528:radiation effects
chemical_list: D000900:Anti-Bacterial Agents; D010640:Phenothiazines; D017319:Photosensitizing Agents