title: Discovery of N-aryl-naphthylamines as in vitro inhibitors of the interaction between HIV integrase and the cofactor LEDGF/p75.
abstract: A series of N-aryl-naphthylamines, exemplified by the structures 11-16, were chosen for an in-house library screening to assay their ability to disrupt the interaction between the LEDGF cofactor and the HIV integrase. Structure modification led also to design and synthesize new compounds 17a-f. Compounds 11e,h,k,n, 13b, and 14 showed good activity in AlphaScreen assay. The most active compound 11e (IC50 = 2.5 μM) was selected for molecular modeling studies and showed a binding mode similar to the one of the known LEDGIN 8.
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" Università di Roma, P-le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Cuzzucoli Crucitti
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" Università di Roma, P-le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Pescatori
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" Università di Roma, P-le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Messore
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" Università di Roma, P-le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Valentina Noemi
authors.initials: VN
authors.lastname: Madia
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" Università di Roma, P-le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pupo
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" Università di Roma, P-le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Saccoliti
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" Università di Roma, P-le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Scipione
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" Università di Roma, P-le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Silvano
authors.initials: S
authors.lastname: Tortorella
authors.affiliation: Dipartimento di Farmacia, Università di Napoli "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Francesco Saverio
authors.initials: FS
authors.lastname: Di Leva
authors.affiliation: DiSTABiF, Seconda Università di Napoli, Via Vivaldi 43, 81100 Caserta, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Cosconati
authors.affiliation: Dipartimento di Farmacia, Università di Napoli "Federico II", Via D. Montesano 49, 80131 Napoli, Italy.
authors.forename: Ettore
authors.initials: E
authors.lastname: Novellino
authors.affiliation: Molecular Virology and Gene Therapy, Molecular Medicine Katholieke Universiteit Leuven, Kapucijnenvoer 33, B-3000 Leuven, Flanders, Belgium.
authors.forename: Zeger
authors.initials: Z
authors.lastname: Debyser
authors.affiliation: Molecular Virology and Gene Therapy, Molecular Medicine Katholieke Universiteit Leuven, Kapucijnenvoer 33, B-3000 Leuven, Flanders, Belgium.
authors.forename: Frauke
authors.initials: F
authors.lastname: Christ
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" Università di Roma, P-le Aldo Moro 5, 00185 Roma, Italy. Electronic address: roberta.costi@uniroma1.it.
authors.forename: Roberta
authors.initials: R
authors.lastname: Costi
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Istituto Pasteur-Fondazione Cenci Bolognetti, "Sapienza" Università di Roma, P-le Aldo Moro 5, 00185 Roma, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Di Santo
mesh_terms: D015057:1-Naphthylamine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D019427:HIV Integrase / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D008958:Models, Molecular; D015394:Molecular Structure; D011485:Protein Binding / Q000187:drug effects; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D062366:para-Aminobenzoates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D019428:HIV Integrase Inhibitors; D036341:Intercellular Signaling Peptides and Proteins; C119380:lens epithelium-derived growth factor; D062366:para-Aminobenzoates; D015057:1-Naphthylamine; D019427:HIV Integrase
keywords: Integrase; LEDGF/p75; LEDGINs; N-aryl-naphthylamine