N,N'-Bisbenzylidenebenzene-1,4-diamines and N,N'-Bisbenzylidenenaphthalene-1,4-diamines as Sirtuin Type 2 (SIRT2) Inhibitors.
A series of N,N'-bisbenzylidenebenzene-1,4-diamine and N,N'-bisbenzylidenenaphthalene-1,4-diamine derivatives were synthesized as inhibitors for human sirtuin type 2 (SIRT2). The design of the new compounds was based on two earlier reported hits from molecular modeling and virtual screening. The most potent compound was N,N'-bis(2-hydroxybenzylidene)benzene-1,4-diamine, which was equipotent with the most potent hit compound and well-known SIRT2 inhibitor sirtinol.
Kiviranta
Päivi H
PH
Department of Pharmaceutical Chemistry , University of Kuopio, P.O. Box 1627, 70211 Kuopio, Finland. paivi.kiviranta@uku.fi
Leppänen
Jukka
J
Kyrylenko
Sergiy
S
Salo
Heikki S
HS
Lahtela-Kakkonen
Maija
M
Tervo
Anu J
AJ
Wittekindt
Carsten
C
Suuronen
Tiina
T
Kuusisto
Erkki
E
Järvinen
Tomi
T
Salminen
Antero
A
Poso
Antti
A
Wallén
Erik A A
EA
D000107:Acetylation; D001665:Binding Sites; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010655:Phenylenediamines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D056565:Sirtuin 2; D037761:Sirtuins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013329:Structure-Activity Relationship
D003959:Diamines; C516689:N,N'-bis(2-hydroxybenzylidene)benzene-1,4-diamine; D010655:Phenylenediamines; C474199:SIRT2 protein, human; D056565:Sirtuin 2; D037761:Sirtuins