Synthesis from Caffeine of a Mixed N-Heterocyclic Carbene−Silver Acetate Complex Active against Resistant Respiratory Pathogens
| Autor: | Abdulkareem Melaiye, Seth D. Crosby, Marvin Coughenour, Christine E. Hovis, Wiley J. Youngs, Amy Milsted, Semih Durmus, Lisa A. Hogue, Carolyn L. Cannon, Claire A. Tessier, Daniel Ely, Aysegul Kascatan-Nebioglu, Matthew J. Panzner, Khadijah M. Hindi, Rebekah J. Mallett |
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| Rok vydání: | 2006 |
| Předmět: |
Antifungal Agents
Cystic Fibrosis Stereochemistry Ethyl acetate Gene Expression Microbial Sensitivity Tests Respiratory Mucosa Acetates Crystallography X-Ray Gram-Positive Bacteria Methylation Medicinal chemistry Chemical synthesis Mice Structure-Activity Relationship chemistry.chemical_compound Drug Resistance Fungal Caffeine Drug Resistance Bacterial Gram-Negative Bacteria Drug Discovery Organometallic Compounds Animals Humans Respiratory Tract Infections Cells Cultured Molecular Structure biology Silver Compounds Biological activity Silver acetate Antimicrobial biology.organism_classification Anti-Bacterial Agents Mice Inbred C57BL Burkholderia cepacia complex chemistry Molecular Medicine Methanol Carbene |
| Zdroj: | Journal of Medicinal Chemistry. 49:6811-6818 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/jm060711t |
| Popis: | The bis(N-heterocyclic carbene) (NHC) silver complex, 3, with a methyl carbonate anion was formed from the reaction of the iodide salt of methylated caffeine, 1, with silver (I) oxide in methanol. Attempts to crystallize this complex from a mixture of common alcohols and ethyl acetate led to the formation of an NHC-silver acetate complex, 4. The more direct synthesis of 4 was accomplished by the in-situ deprotonation of 1 by silver acetate in methanol. Complex 4 demonstrated antimicrobial activity against numerous resistant respiratory pathogens from the lungs of cystic fibrosis (CF) patients including members of the Burkholderia cepacia complex that cause a high rate of mortality in patients with cystic fibrosis (CF). Application of this NHC silver complex to primary cultures of murine respiratory epithelial cells followed by microarray analysis showed minimal gene expression changes at the concentrations effective against respiratory pathogens. Furthermore, methylated caffeine without silver showed some antibacterial and antifungal activity. |
| Databáze: | OpenAIRE |
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