N-Hydroxy-(4-oxime)-cinnamide: a versatile scaffold for the synthesis of novel histone deacetylase [correction of deacetilase] (HDAC) inhibitors.
With the aim to discover novel HDAC inhibitors with high potency and good safety profiles, we have designed a small library based on a N-hydroxy-(4-oxime)-cinnamide scaffold. We describe the synthesis of these novel compounds and some preliminary in vitro cytotoxic activity on three tumor cell lines, NB4, H460 and HCT116, as well as their inhibitory activity against class I, II and IV HDAC. Several 4-oxime derivatives demonstrated a promising inhibitory activity on HDAC6 and HDAC8 coupled to a good selectivity profile.
Giannini
Giuseppe
G
R&D Sigma-Tau SpA, Pomezia, Italy. giuseppe.giannini@sigma-tau.it
Marzi
Mauro
M
Pezzi
Riccardo
R
Brunetti
Tiziana
T
Battistuzzi
Gianfranco
G
Marzo
Maria Di
MD
Cabri
Walter
W
Vesci
Loredana
L
Pisano
Claudio
C
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D002934:Cinnamates / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000145:classification / Q000378:metabolism; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000145:classification / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology
D000970:Antineoplastic Agents; D002934:Cinnamates; D056572:Histone Deacetylase Inhibitors; D007527:Isoenzymes; D006655:Histone Deacetylases