Exploring alternative Zn-binding groups in the design of HDAC inhibitors: squaric acid, N-hydroxyurea, and oxazoline analogues of SAHA.
Analogues of suberoylanilide hydroxamic acid (SAHA) were prepared by replacing the Zn-binding group with squaric acid, N-hydroxyurea, and 4-hydroxymethyl oxazoline units, also varying the length of the aliphatic chain. No inhibitory activity on HDAC was observed below 1.0 microM and no cytotoxic activity on different tumor cell lines was seen below 20.0 microM.
Hanessian
Stephen
S
Department of Chemistry, Université de Montréal, PO Box 6128, Station Centre-ville, Montréal, Que., Canada H3C 3J7. stephen.hanessian@umontreal.ca
Vinci
Valerio
V
Auzzas
Luciana
L
Marzi
Mauro
M
Giannini
Giuseppe
G
D000480:Alkynes / Q000737:chemistry*; D003503:Cyclobutanes / Q000737:chemistry*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006918:Hydroxyurea / Q000737:chemistry*; D015394:Molecular Structure; D010080:Oxazoles / Q000737:chemistry*; D000077337:Vorinostat; D015032:Zinc / Q000737:chemistry*
D000480:Alkynes; D003503:Cyclobutanes; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D010080:Oxazoles; D000077337:Vorinostat; D006655:Histone Deacetylases; D015032:Zinc; C030042:squaric acid; D006918:Hydroxyurea