title: S-Nitrosothiol-modified nitric oxide-releasing chitosan oligosaccharides as antibacterial agents.
abstract: S-Nitrosothiol-modified chitosan oligosaccharides were synthesized by reaction with 2-iminothiolane hydrochloride and 3-acetamido-4,4-dimethylthietan-2-one, followed by thiol nitrosation. The resulting nitric oxide (NO)-releasing chitosan oligosaccharides stored ∼0.3μmol NO mg(-1) chitosan. Both the chemical structure of the nitrosothiol (i.e. primary and tertiary) and the use of ascorbic acid as a trigger for NO donor decomposition were used to control the NO-release kinetics. With ascorbic acid, the S-nitrosothiol-modified chitosan oligosaccharides elicited a 4-log reduction in Pseudomonas aeruginosa viability. Confocal microscopy indicated that the primary S-nitrosothiol-modified chitosan oligosaccharides associated more with the bacteria relative to the tertiary S-nitrosothiol system. The primary S-nitrosothiol-modified chitosan oligosaccharides elicited minimal toxicity towards L929 mouse fibroblast cells at the concentration necessary for a 4-log reduction in bacterial viability, further demonstrating the potential of S-nitrosothiol-modified chitosan oligosaccharides as NO-release therapeutics.
authors.affiliation: Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Anand
authors.initials: A
authors.lastname: Shah
authors.affiliation: Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Hunter
authors.affiliation: Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Soto
authors.affiliation: Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA. Electronic address: schoenfisch@unc.edu.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Schoenfisch
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D048271:Chitosan / Q000737:chemistry*; D005347:Fibroblasts / Q000187:drug effects; D051379:Mice; D009569:Nitric Oxide / Q000737:chemistry*; D009844:Oligosaccharides / Q000737:chemistry / Q000494:pharmacology*; D066244:Proton Magnetic Resonance Spectroscopy; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D026403:S-Nitrosothiols / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D009844:Oligosaccharides; D026403:S-Nitrosothiols; D009569:Nitric Oxide; D048271:Chitosan
keywords: Ascorbic acid; Chitosan; Nitric oxide; S-Nitrosothiol; Synergy