Design, Palladium-Catalyzed Synthesis, and Biological Investigation of 2-Substituted 3-Aroylquinolin-4(1H)-ones as Inhibitors of the Hedgehog Signaling Pathway

Romina Alfonsi; Bruno Botta; Sandro Cacchi; Lucia Di Marcotullio; Giancarlo Fabrizi; Roberta Faedda; Antonella Goggiamani; Antonia Iazzetti; Mattia Mori

doi:10.1021/acs.jmedchem.6b01135

Design, Palladium-Catalyzed Synthesis, and Biological Investigation of 2-Substituted 3-Aroylquinolin-4(1H)-ones as Inhibitors of the Hedgehog Signaling Pathway

Romina Alfonsi
, Bruno Botta
, Sandro Cacchi
, Lucia Di Marcotullio
, Giancarlo Fabrizi
, Roberta Faedda
, Antonella Goggiamani^*
, Antonia Iazzetti
, Mattia Mori

^*Corresponding author

Research output: Contribution to journal › Article

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.

Original language	English
Pages (from-to)	1469-1477
Number of pages	9
Journal	Journal of Medicinal Chemistry
Volume	60
DOIs	https://doi.org/10.1021/acs.jmedchem.6b01135
Publication status	Published - 2017

Keywords

Animals
Antineoplastic Agents
Catalysis
Cell Line
Cell Line, Tumor
Cell Proliferation
Drug Design
Hedgehog Proteins
Humans
Mice
Models, Molecular
Neoplasms
Palladium
Quinolones
Signal Transduction

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10.1021/acs.jmedchem.6b01135

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Alfonsi, R., Botta, B., Cacchi, S., Di Marcotullio, L., Fabrizi, G., Faedda, R., Goggiamani, A., Iazzetti, A., & Mori, M. (2017). Design, Palladium-Catalyzed Synthesis, and Biological Investigation of 2-Substituted 3-Aroylquinolin-4(1H)-ones as Inhibitors of the Hedgehog Signaling Pathway. Journal of Medicinal Chemistry, 60, 1469-1477. https://doi.org/10.1021/acs.jmedchem.6b01135

@article{7dda28004a3640c6925af0c8c9442b48,

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.",

keywords = "Animals, Antineoplastic Agents, Catalysis, Cell Line, Cell Line, Tumor, Cell Proliferation, Drug Design, Hedgehog Proteins, Humans, Mice, Models, Molecular, Neoplasms, Palladium, Quinolones, Signal Transduction, Animals, Antineoplastic Agents, Catalysis, Cell Line, Cell Line, Tumor, Cell Proliferation, Drug Design, Hedgehog Proteins, Humans, Mice, Models, Molecular, Neoplasms, Palladium, Quinolones, Signal Transduction",

author = "Romina Alfonsi and Bruno Botta and Sandro Cacchi and \{Di Marcotullio\}, Lucia and Giancarlo Fabrizi and Roberta Faedda and Antonella Goggiamani and Antonia Iazzetti and Mattia Mori",

year = "2017",

doi = "10.1021/acs.jmedchem.6b01135",

language = "English",

volume = "60",

pages = "1469--1477",

journal = "Journal of Medicinal Chemistry",

issn = "0022-2623",

publisher = "American Chemical Society",

}

Alfonsi, R, Botta, B, Cacchi, S, Di Marcotullio, L, Fabrizi, G, Faedda, R, Goggiamani, A, Iazzetti, A & Mori, M 2017, 'Design, Palladium-Catalyzed Synthesis, and Biological Investigation of 2-Substituted 3-Aroylquinolin-4(1H)-ones as Inhibitors of the Hedgehog Signaling Pathway', Journal of Medicinal Chemistry, vol. 60, pp. 1469-1477. https://doi.org/10.1021/acs.jmedchem.6b01135

TY - JOUR

T1 - Design, Palladium-Catalyzed Synthesis, and Biological Investigation of 2-Substituted 3-Aroylquinolin-4(1H)-ones as Inhibitors of the Hedgehog Signaling Pathway

AU - Alfonsi, Romina

AU - Botta, Bruno

AU - Cacchi, Sandro

AU - Di Marcotullio, Lucia

AU - Fabrizi, Giancarlo

AU - Faedda, Roberta

AU - Goggiamani, Antonella

AU - Iazzetti, Antonia

AU - Mori, Mattia

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Animals

KW - Antineoplastic Agents

KW - Catalysis

KW - Cell Line

KW - Cell Line, Tumor

KW - Cell Proliferation

KW - Drug Design

KW - Hedgehog Proteins

KW - Humans

KW - Mice

KW - Models, Molecular

KW - Neoplasms

KW - Palladium

KW - Quinolones

KW - Signal Transduction

KW - Animals

KW - Antineoplastic Agents

KW - Catalysis

KW - Cell Line

KW - Cell Line, Tumor

KW - Cell Proliferation

KW - Drug Design

KW - Hedgehog Proteins

KW - Humans

KW - Mice

KW - Models, Molecular

KW - Neoplasms

KW - Palladium

KW - Quinolones

KW - Signal Transduction

UR - http://hdl.handle.net/10807/200504

U2 - 10.1021/acs.jmedchem.6b01135

DO - 10.1021/acs.jmedchem.6b01135

M3 - Article

SN - 0022-2623

VL - 60

SP - 1469

EP - 1477

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

ER -

Design, Palladium-Catalyzed Synthesis, and Biological Investigation of 2-Substituted 3-Aroylquinolin-4(1H)-ones as Inhibitors of the Hedgehog Signaling Pathway

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Keywords

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