title: Synthesis and properties of benzo[a]phenoxazinium chalcogen analogues as novel broad-spectrum antimicrobial photosensitizers.
abstract: The goal of this investigation was to develop improved photosensitizers for use as antimicrobial drugs in photodynamic therapy of localized infections. Replacement of the oxygen atom in 5-(ethylamino)-9-diethylaminobenzo[a]phenoxazinium chloride (1) with sulfur and selenium afforded thiazinium and selenazinium analogues 2 and 3, respectively. All three dyes are water soluble, lipophilic, and red light absorbers. The relative photodynamic activities of the chalcogen series were evaluated against a panel of prototypical pathogenic microorganisms: the Gram-positive Enterococcus faecalis, the Gram-negative Escherichia coli, and the fungus Candida albicans. Selenium dye 3 was highly effective as a broad-spectrum antimicrobial photosensitizer with fluences of 4-32 J/cm2 killing 2-5 more logs of all cell types than sulfur dye 2, which was slightly more effective than oxygen analogue 1. These data, taken with the findings of uptake and retention studies, suggest that the superior activity of selenium derivative 3 can be attributed to its much higher triplet quantum yield.
authors.affiliation: Rowland Institute at Harvard, Harvard University, Cambridge, Massachusetts 02142, USA. foley@rowland.harvard.edu
authors.forename: James W
authors.initials: JW
authors.lastname: Foley
authors.forename: Xiangzhi
authors.initials: X
authors.lastname: Song
authors.forename: Tatiana N
authors.initials: TN
authors.lastname: Demidova
authors.forename: Fatima
authors.initials: F
authors.lastname: Jalil
authors.forename: Fatima
authors.initials: F
authors.lastname: Jilal
authors.forename: Michael R
authors.initials: MR
authors.lastname: Hamblin
mesh_terms: D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001665:Binding Sites; D002176:Candida albicans / Q000166:cytology / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D018011:Chalcogens / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010078:Oxazines / Q000737:chemistry*; D017319:Photosensitizing Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D018011:Chalcogens; D010078:Oxazines; D017319:Photosensitizing Agents; C039203:phenoxazine