Omega-alkoxy analogues of SAHA (vorinostat) as inhibitors of HDAC: a study of chain-length and stereochemical dependence.
A series of omega-alkoxy ethers were prepared with variation of the length of the aliphatic chain of suberoylanilide hydroxamic acid (SAHA, vorinostat). Eight carbon long chain analogues showed the best activity, among which several substituted benzyl ether derivatives exhibited inhibitory activity on HDAC comparable to SAHA, and antiproliferative activity on three human cell lines (NB4, H460, and HCT-116) better than SAHA. However, no significant difference in antiproliferative activity was observed between two enantiomers bearing the benzyl ether moiety.
Hanessian
Stephen
S
Department of Chemistry, Université de Montréal, Station Centre-ville, Montréal, Quebec, Canada. stephen.hanessian@umontreal.ca
Auzzas
Luciana
L
Giannini
Giuseppe
G
Marzi
Mauro
M
Cabri
Walter
W
Barbarino
Marcella
M
Vesci
Loredana
L
Pisano
Claudio
C
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001554:Benzene / Q000737:chemistry; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004987:Ethers / Q000737:chemistry; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D000077337:Vorinostat
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D004987:Ethers; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat; D001554:Benzene