Novel uracil-based 2-aminoanilide and 2-aminoanilide-like derivatives: histone deacetylase inhibition and in-cell activities.
A novel series of non-hydroxamate HDAC inhibitors (HDACi) showing a uracil group at the left and a 2-aminoanilide/2-aminoanilide-like portion at the right head have been reported. In particular, the new compounds incorporating a 2-aminoanilide moiety behaved as class I-selective HDACi. Compound 8, the most potent and class I-selective, showed weak apoptosis (higher than MS-275) joined to cytodifferentiating activity on U937 cells. Surprisingly, the highest differentiation was observed with 13, through an effect that seems to be unrelated to HDAC inhibition.
Mai
Antonello
A
Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Studi Farmaceutici, Sapienza Università di Roma, P.le A. Moro 5, 00185 Roma, Italy. antonello.mai@uniroma1.it
Perrone
Andrea
A
Nebbioso
Angela
A
Rotili
Dante
D
Valente
Sergio
S
Tardugno
Maria
M
Massa
Silvio
S
De Bellis
Floriana
F
Altucci
Lucia
L
D000107:Acetylation; D000586:Amination; D001550:Benzamidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D006098:Granulocytes / Q000166:cytology / Q000187:drug effects; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D020298:U937 Cells; D014498:Uracil / Q000737:chemistry / Q000494:pharmacology*
D001550:Benzamidines; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D011994:Recombinant Proteins; D014498:Uracil; D006655:Histone Deacetylases