Inhibitors of Sir2: Evaluation of Splitomicin Analogues. Posakony, J., Hirao, M., Stevens, S., a Simon, J., & Bedalov, A. Journal of medicinal chemistry, 47(10):2635–44, May, 2004.
doi  abstract   bibtex   
Splitomicin (1) and 41 analogues were prepared and evaluated in cell-based Sir2 inhibition and toxicity assays and an in vitro Sir2 inhibition assay. Lactone ring or naphthalene (positions 7-9) substituents decrease activity, but other naphthalene substitutions (positions 5 and 6) are well-tolerated. The hydrolytically unstable aromatic lactone is important for activity. Lactone hydrolysis rates were used as a measure of reactivity; hydrolysis rates correlate with inhibitory activity. The most potent Sir2 inhibitors were structurally similar to and had hydrolysis rates similar to 1.
@article{Posakony2004,
  title = {Inhibitors of {{Sir2}}: Evaluation of Splitomicin Analogues.},
  author = {Posakony, Jeff and Hirao, Maki and Stevens, Sam and a Simon, Julian and Bedalov, Antonio},
  year = {2004},
  month = may,
  journal = {Journal of medicinal chemistry},
  volume = {47},
  number = {10},
  eprint = {15115404},
  eprinttype = {pubmed},
  pages = {2635--44},
  issn = {0022-2623},
  doi = {10.1021/jm030473r},
  abstract = {Splitomicin (1) and 41 analogues were prepared and evaluated in cell-based Sir2 inhibition and toxicity assays and an in vitro Sir2 inhibition assay. Lactone ring or naphthalene (positions 7-9) substituents decrease activity, but other naphthalene substitutions (positions 5 and 6) are well-tolerated. The hydrolytically unstable aromatic lactone is important for activity. Lactone hydrolysis rates were used as a measure of reactivity; hydrolysis rates correlate with inhibitory activity. The most potent Sir2 inhibitors were structurally similar to and had hydrolysis rates similar to 1.},
  isbn = {2066676241},
  pmid = {15115404},
  keywords = {\#nosource,Histone Deacetylase Inhibitors,Lactones,Lactones: chemistry,Naphthalenes,Naphthalenes: chemical synthesis,Naphthalenes: chemistry,Naphthalenes: pharmacology,Pyrones,Pyrones: chemical synthesis,Pyrones: chemistry,Pyrones: pharmacology,Saccharomyc,Saccharomyces cerevisiae,Saccharomyces cerevisiae: drug effects,Saccharomyces cerevisiae: enzymology,Silent Information Regulator Proteins,Sirtuin 2,Sirtuins,Sirtuins: antagonists \& inhibitors,Structure-Activity Relationship}
}

Downloads: 0