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}
}
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