Synthesis and biological characterisation of sirtuin inhibitors based on the tenovins.
The tenovins are small molecule inhibitors of the NAD(+)-dependent family of protein deacetylases known as the sirtuins. There remains considerable interest in inhibitors of this enzyme family due to possible applications in both cancer and neurodegenerative disease therapy. Through the synthesis of novel tenovin analogues, further insights into the structural requirements for activity against the sirtuins in vitro are provided. In addition, the activity of one of the analogues in cells led to an improved understanding of the function of SirT1 in cells.
School of Chemistry and Biomedical Sciences Research Complex, University of St. Andrews, North Haugh, St. Andrews, Fife, UK.
Anna R
AR
McCarthy
Lisa
L
Pirrie
Jonathan J
JJ
Hollick
Sebastien
S
Ronseaux
Johanna
J
Campbell
Maureen
M
Higgins
Oliver D
OD
Staples
Fanny
F
Tran
Alexandra M Z
AM
Slawin
Sonia
S
Lain
Nicholas J
NJ
Westwood
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D006860:Hydrogen Bonding; D061986:MCF-7 Cells; D008968:Molecular Conformation; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; C574854:tenovin-6; D037761:Sirtuins