Synthesis from caffeine of a mixed N-heterocyclic carbene-silver acetate complex active against resistant respiratory pathogens

Aysegul Kascatan-Nebioglu, Abdulkareem Melaiye, Khadijah Hindi, Semih Durmus, Matthew J. Panzner, Lisa A. Hogue, Rebekah J. Mallett, Christine E. Hovis, Marvin Coughenour, Seth D. Crosby, Amy Milsted, Daniel L. Ely, Claire A. Tessier, Carolyn L. Cannon, Wiley J. Youngs

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Abstract

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.

Original languageEnglish
Pages (from-to)6811-6818
Number of pages8
JournalJournal of Medicinal Chemistry
Volume49
Issue number23
DOIs
StatePublished - Nov 16 2006

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    Kascatan-Nebioglu, A., Melaiye, A., Hindi, K., Durmus, S., Panzner, M. J., Hogue, L. A., Mallett, R. J., Hovis, C. E., Coughenour, M., Crosby, S. D., Milsted, A., Ely, D. L., Tessier, C. A., Cannon, C. L., & Youngs, W. J. (2006). Synthesis from caffeine of a mixed N-heterocyclic carbene-silver acetate complex active against resistant respiratory pathogens. Journal of Medicinal Chemistry, 49(23), 6811-6818. https://doi.org/10.1021/jm060711t