Identification of 4-hydroxyquinolines inhibitors of p300/CBP histone acetyltransferases.
We identified a series of 4-hydroxyquinolines bearing a C1 to C15 alkyl chain at the C2 position and a carbethoxy/carboxy group at the C3 position of the quinoline nucleus (MC compounds), endowed with selective inhibitory activity against the p300/CBP HAT enzymes. Enzyme inhibition was investigated using in vitro HAT assays and by western blot analysis of cellular lysates to examine the acetylation levels of histone H3 and alpha-tubulin. When tested in U937 cells, some compounds displayed pro-apoptotic or cytodifferentiating properties.
Mai
Antonello
A
Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza Università di Roma, P.le A. Moro 5, 00185 Roma, Italy. antonello.mai@uniroma1.it
Rotili
Dante
D
Tarantino
Domenico
D
Nebbioso
Angela
A
Castellano
Sabrina
S
Sbardella
Gianluca
G
Tini
Marc
M
Altucci
Lucia
L
D020650:Combinatorial Chemistry Techniques; D051548:Histone Acetyltransferases / Q000037:antagonists & inhibitors*; D006801:Humans; D006912:Hydroxyquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D050880:p300-CBP Transcription Factors / Q000037:antagonists & inhibitors*
D006912:Hydroxyquinolines; D051548:Histone Acetyltransferases; D050880:p300-CBP Transcription Factors