A theobromine derived silver N-heterocyclic carbene: synthesis, characterization, and antimicrobial efficacy studies on cystic fibrosis relevant pathogens.
The increasing incidence of multidrug-resistant (MDR) pulmonary infections in the cystic fibrosis (CF) population has prompted the investigation of innovative silver based therapeutics. The functionalization of the naturally occurring xanthine theobromine at the N(1) nitrogen atom with an ethanol substituent followed by the methylation of the N(9) nitrogen atom gives the N-heterocyclic carbene precursor 1-(2-hydroxyethyl)-3,7,9-trimethylxanthinium iodide. The reaction of this xanthinium salt with silver acetate produces the highly hydrophilic silver carbene complex SCC8. The in vitro antimicrobial efficacy of this newly synthesized complex was evaluated with excellent results on a variety of virulent and MDR pathogens isolated from CF patients. A comparative in vivo study between the known caffeine derived silver carbene SCC1 and SCC8 demonstrated the ability of both complexes to improve the survival rates of mice in a pneumonia model utilizing the clinically isolated infectious strain of Pseudomonas aeruginosa PA M57-15.
Panzner
Matthew J
MJ
Department of Chemistry, The University of Akron, Akron, OH 44325-3601, USA.
Hindi
Khadijah M
KM
Wright
Brian D
BD
Taylor
Jane B
JB
Han
Daniel S
DS
Youngs
Wiley J
WJ
Cannon
Carolyn L
CL
D000818:Animals; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D003550:Cystic Fibrosis / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D006571:Heterocyclic Compounds / Q000737:chemistry; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D008826:Microbial Sensitivity Tests; D008958:Models, Molecular; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity; D012834:Silver / Q000737:chemistry*; D013237:Stereoisomerism; D013805:Theobromine / Q000737:chemistry*
D000900:Anti-Bacterial Agents; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; C030011:carbene; D012834:Silver; D013805:Theobromine; D008697:Methane
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