title: Quinoline-based p300 histone acetyltransferase inhibitors with pro-apoptotic activity in human leukemia U937 cells.
abstract: Chemical manipulations performed on 2-methyl-3-carbethoxyquinoline (1), a histone acetyltransferase inhibitor previously identified by our research group and active at the sub-millimolar/millimolar level, led to compounds bearing higher alkyl groups at the C2-quinoline or additional side chains at the C6-quinoline positions. Such compounds displayed at least threefold improved inhibitory potency toward p300 protein lysine acetyltransferase activity; some of them decreased histone H3 and H4 acetylation levels in U937 cells and induced high degrees of apoptosis (three compounds >10-fold higher than compound 1) after treatment of U937 cells.
authors: Department of Drug Chemistry & Technologies, Sapienza University of Rome, P.le Aldo Moro 5, 00185 Rome (Italy).
authors: Alessia
authors: A
authors: Lenoci
authors: Stefano
authors: S
authors: Tomassi
authors: Mariarosaria
authors: M
authors: Conte
authors: Rosaria
authors: R
authors: Benedetti
authors: Veronica
authors: V
authors: Rodriguez
authors: Simone
authors: S
authors: Carradori
authors: Daniela
authors: D
authors: Secci
authors: Sabrina
authors: S
authors: Castellano
authors: Gianluca
authors: G
authors: Sbardella
authors: Patrizia
authors: P
authors: Filetici
authors: Ettore
authors: E
authors: Novellino
authors: Lucia
authors: L
authors: Altucci
authors: Dante
authors: D
authors: Rotili
authors: Antonello
authors: A
authors: Mai
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D011804:Quinolines; C037219:quinoline
keywords: apoptosis; epigenetics; leukemia; lysine acetyltransferases (KATs); p300; structure-activity relationships