title: Antimicrobial activity of water-soluble triazole phenazine clickamers against E. coli.
abstract: The antimicrobial potency of phenazine derivatives is attenuated by their inherently hydrophobic nature, complicating their use as antibiotic drugs. We have analyzed the cytotoxicity and mode of action of water-soluble bis-triazolyl phenazines against E. coli and a human epithelial (HaCat) cell line. We observed complete inhibition of bacterial growth over concentration ranges that do not affect the viability of human epithelial cells. Confocal fluorescence microscopy revealed a high degree of interaction between the phenazine compounds and E. coli, as well as evidence of membrane damage in phenazine-treated E. coli. Additional data suggests that the potency of these particular water-soluble phenazine compounds does not result from the production of reactive oxygen species, but rather from cytotoxic interference with metabolic electron-transfer cascades.
authors: Organisch-Chemisches Institut, Ruprecht-Karls-Universität Heidelberg, Im Neuenheimer Feld 270, 69120 Heidelberg (Germany), Fax: (+49) 6221548401; School of Chemistry and Biochemistry, Georgia Institute of Technology, 901 Atlantic Drive, Atlanta, GA 30332-0400 (USA).
authors: Steven C
authors: SC
authors: Hayden
authors: Jonathan J
authors: JJ
authors: Bryant
authors: Megan A
authors: MA
authors: Mackey
authors: Katharina
authors: K
authors: Höfer
authors: Benjamin D
authors: BD
authors: Lindner
authors: Vanessa P
authors: VP
authors: Nguyen
authors: Andres
authors: A
authors: Jäschke
authors: Uwe H F
authors: UH
authors: Bunz
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects*; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D010619:Phenazines / Q000737:chemistry*; D011789:Quantum Theory; D017382:Reactive Oxygen Species / Q000378:metabolism; D014230:Triazoles / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D000890:Anti-Infective Agents; D010619:Phenazines; D017382:Reactive Oxygen Species; D014230:Triazoles; D014867:Water
keywords: Escherichia coli; antimicrobial; phenazines; redox cycling; water soluble