Identification of tri- and tetracyclic pyrimidinediones as sirtuin inhibitors.
CHEMMEDCHEM(2010)
Abstract
Sirtuins are deacetylase proteins that regulate transcription, genome maintenance, longevity, and metabolism. Eight compounds were identified as a novel class of sirtuin inhibitors, with 5, 7, and 9 being the most effective as SIRT1-selective inhibitors. In U937 cells 5 induced apoptosis and displayed antiproliferative effects in Raji, DLD1, and HeLa cancer cells, suggesting potential utility in cancer treatment.
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Key words
antiproliferation,apoptosis,diazabenzoanthracene,inhibitors,sirtuins
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