title: Design, Palladium-Catalyzed Synthesis, and Biological Investigation of 2-Substituted 3-Aroylquinolin-4(1H)-ones as Inhibitors of the Hedgehog Signaling Pathway.
abstract: 2-Substituted 3-aroylquinolin-4(1H)-ones, prepared through a palladium-catalyzed carbonylative cyclization of N-(2-iodoaryl)enaminones, proved to inhibit efficiently the Hedgehog pathway through direct antagonism of the wild-type and drug-resistant form of the Smoothened receptor. Notably, these compounds repressed the Hh-dependent growth events and the proliferation of tumor cells with aberrant activation of the Hh pathway, which plays a crucial role in development and tumorigenesis.
authors.affiliation: Department of Molecular Medicine, Sapienza University , Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Romina
authors.initials: R
authors.lastname: Alfonsi
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University , Piazzale A. Moro 5, 00185 Rome, Italy.
authors.forename: Bruno
authors.identifier: 0000-0001-8707-4333
authors.initials: B
authors.lastname: Botta
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University , Piazzale A. Moro 5, 00185 Rome, Italy.
authors.forename: Sandro
authors.initials: S
authors.lastname: Cacchi
authors.affiliation: Department of Molecular Medicine, Sapienza University , Viale Regina Elena 291, 00161 Rome, Italy.|Istituto Pasteur, Fondazione Cenci-Bolognetti, Sapienza University , Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Di Marcotullio
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University , Piazzale A. Moro 5, 00185 Rome, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Fabrizi
authors.affiliation: Department of Molecular Medicine, Sapienza University , Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Faedda
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University , Piazzale A. Moro 5, 00185 Rome, Italy.
authors.forename: Antonella
authors.identifier: 0000-0001-8339-4284
authors.initials: A
authors.lastname: Goggiamani
authors.affiliation: Dipartimento di Chimica e Tecnologie del Farmaco, Sapienza University , Piazzale A. Moro 5, 00185 Rome, Italy.
authors.forename: Antonia
authors.initials: A
authors.lastname: Iazzetti
authors.affiliation: Center for Life Nano Science@Sapienza, Istituto Italiano di Tecnologia , Viale Regina Elena 291, 00161 Rome, Italy.
authors.forename: Mattia
authors.initials: M
authors.lastname: Mori
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D010165:Palladium / Q000737:chemistry; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D053823:Hedgehog Proteins; D015363:Quinolones; D010165:Palladium