title: Nitric oxide-releasing dendrimers as antibacterial agents.
abstract: The antibacterial activity of a series of nitric oxide (NO)-releasing poly(propylene imine) (PPI) dendrimers was evaluated against both Gram-positive and Gram-negative pathogenic bacteria, including methicillin-resistant  Staphylococcus aureus . A direct comparison of the bactericidal efficacy between NO-releasing and control PPI dendrimers (i.e., non-NO-releasing) revealed both enhanced biocidal action of NO-releasing dendrimers and reduced toxicity against mammalian fibroblast cells. Antibacterial activity for the NO donor-functionalized PPI dendrimers was shown to be a function of both dendrimer size (molecular weight) and exterior functionality. In addition to minimal toxicity against fibroblasts, NO-releasing PPI dendrimers modified with styrene oxide exhibited the greatest biocidal activity (≥99.999% killing) against all bacterial strains tested. The N-diazeniumdiolate NO donor-functionalized PPI dendrimers presented in this study hold promise as effective NO-based therapeutics for combating bacterial infections.
authors.affiliation: Department of Chemistry, University of North Carolina, Chapel Hill, NC 27599, USA.
authors.forename: Bin
authors.initials: B
authors.lastname: Sun
authors.forename: Danielle L
authors.initials: DL
authors.lastname: Slomberg
authors.forename: Shalini L
authors.initials: SL
authors.lastname: Chudasama
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.forename: Mark H
authors.initials: MH
authors.lastname: Schoenfisch
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001391:Azo Compounds / Q000737:chemistry; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D050091:Dendrimers / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005347:Fibroblasts / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009569:Nitric Oxide / Q000737:chemistry*; D011126:Polypropylenes / Q000737:chemistry / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D001391:Azo Compounds; D050091:Dendrimers; D011126:Polypropylenes; C452539:diazeniumdiolate; C443641:poly(propyleneimine); D009569:Nitric Oxide