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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Inhibitors of Sir2: evaluation of splitomicin analogues.

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.[1]

References

  1. Inhibitors of Sir2: evaluation of splitomicin analogues. Posakony, J., Hirao, M., Stevens, S., Simon, J.A., Bedalov, A. J. Med. Chem. (2004) [Pubmed]
 
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