Structure-activity relationship studies of novel oxygen-incorporated SAHA analogues.
Novel oxygen-incorporated SAHA (oxa-SAHA) analogues, in which oxygen was inserted in the alkyl linker connecting the hydroxamic acid moiety and amide group, were synthesized and their inhibitory activities on histone deacetylase were evaluated. The most active oxa-SAHA analogue potently inhibited histone deacetylase, almost as potently as SAHA. Various structural modifications in the amide, but not the hydroxamic acid, significantly affected the inhibitory activities of the derivatives. Based on the inhibitory data, the N-phenyl moiety of the amide turned to be a better modification site for enhancing the inhibitory activity.
Kim
Soon-Ai
SA
Genome Research Center for Immune Disorders, College of Medicine, Wonkwang University, Iksan, 570-749, South Korea.
Jin
Ying Lan
YL
Kim
Hak Sung
HS
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D000077337:Vorinostat
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat