Discovery of (aryloxopropenyl)pyrrolyl hydroxyamides as selective inhibitors of class IIa histone deacetylase homologue HD1-A.
Chemical manipulations performed on aroyl pyrrolyl hydroxyamides, a new class of HDAC inhibitors previously reported by us, led to (aryloxopropenyl)pyrrolyl hydroxyamides 3a-g. Such compounds, showing better inhibitory activity against maize HD1-A than HD1-B (two homologues of mammalian class IIa and I HDACs, respectively), are the first class of IIa-selective inhibitors (fold selectivity: 7-78). They could be useful as tools for probing the biology of these enzymes and eventually as new anticancer agents with low toxicity.
Dipartimento di Studi Farmaceutici, Università degli Studi di Roma "La Sapienza", P. le A. Moro 5, 00185 Roma, Italy. antonello.mai@uniroma1.it
Antonello
A
Mai
Silvio
S
Massa
Riccardo
R
Pezzi
Dante
D
Rotili
Peter
P
Loidl
Gerald
G
Brosch
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D056572:Histone Deacetylase Inhibitors; D011422:Propionates / Q000138:chemical synthesis* / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
D000577:Amides; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D011422:Propionates; D011758:Pyrroles