Squaramides as novel class I and IIB histone deacetylase inhibitors for topical treatment of cutaneous t-cell lymphoma.

Fournier, Jean-François; Bhurruth-Alcor, Yushma; Musicki, Branislav; Aubert, Jérome; Aurelly, Michèle; Bouix-Peter, Claire; Bouquet, Karinne; Chantalat, Laurent; Delorme, Marion; Drean, Bénédicte; Duvert, Gwenaelle; Fleury-Bregeot, Nicolas; Gauthier, Blanche; Grisendi, Karine; Harris, Craig S; Hennequin, Laurent F; Isabet, Tatiana; Joly, Florence; Lafitte, Guillaume; Millois, Corinne; Morgentin, Rémy; Pascau, Jonathan; Piwnica, David; Rival, Yves; Soulet, Catherine; Thoreau, Étienne; Tomas, Loïc

Fournier, Jean-François; Bhurruth-Alcor, Yushma; Musicki, Branislav; Aubert, Jérome; Aurelly, Michèle; Bouix-Peter, Claire; Bouquet, Karinne; Chantalat, Laurent; Delorme, Marion; Drean, Bénédicte; Duvert, Gwenaelle; Fleury-Bregeot, Nicolas; Gauthier, Blanche; Grisendi, Karine; Harris, Craig S; Hennequin, Laurent F; Isabet, Tatiana; Joly, Florence; Lafitte, Guillaume; Millois, Corinne; Morgentin, Rémy; Pascau, Jonathan; Piwnica, David; Rival, Yves; Soulet, Catherine; Thoreau, Étienne; Tomas, Loïc.

Afiliação

Fournier JF; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France. Electronic address: jean-francois.fournier@umontreal.ca.
Bhurruth-Alcor Y; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Musicki B; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Aubert J; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Aurelly M; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Bouix-Peter C; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Bouquet K; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Chantalat L; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Delorme M; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Drean B; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Duvert G; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Fleury-Bregeot N; Edelris, 115 Avenue Lacassagne, 69003 Lyon, France.
Gauthier B; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Grisendi K; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Harris CS; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Hennequin LF; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Isabet T; Synchrotron Soleil, L'Orme des Merisiers, Saint-Aubin - BP 48, 91192 Gif-sur-Yvette Cedex, France.
Joly F; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Lafitte G; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Millois C; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Morgentin R; Edelris, 115 Avenue Lacassagne, 69003 Lyon, France.
Pascau J; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Piwnica D; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Rival Y; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Soulet C; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Thoreau É; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.
Tomas L; Nestlé Skin Health R&D, 2400 Route des colles, BP 87, 06902 Sophia-Antipolis Cedex, France.

Bioorg Med Chem Lett ; 28(17): 2985-2992, 2018 09 15.

Article em En | MEDLINE | ID: mdl-30122227

ABSTRACT

ABSTRACT

A series of squaramide-based hydroxamic acids were designed, synthesized and evaluated against human HDAC enzyme. Squaramides were found to be potent in the Hut78 cell line, but initially suffered from low solubility. Leads with improved solubility and metabolic profiles were shown to be class I, IIB and IV selective.

Assuntos

Antineoplásicos/farmacologia; Histona Desacetilase 1/antagonistas & inibidores; Histona Desacetilase 2/antagonistas & inibidores; Inibidores de Histona Desacetilases/farmacologia; Linfoma Cutâneo de Células T/tratamento farmacológico; Quinina/análogos & derivados; Neoplasias Cutâneas/tratamento farmacológico; Antineoplásicos/síntese química; Antineoplásicos/química; Apoptose/efeitos dos fármacos; Linhagem Celular Tumoral; Proliferação de Células/efeitos dos fármacos; Cristalografia por Raios X; Relação Dose-Resposta a Droga; Ensaios de Seleção de Medicamentos Antitumorais; Histona Desacetilase 1/metabolismo; Histona Desacetilase 2/metabolismo; Inibidores de Histona Desacetilases/síntese química; Inibidores de Histona Desacetilases/química; Humanos; Linfoma Cutâneo de Células T/metabolismo; Linfoma Cutâneo de Células T/patologia; Modelos Moleculares; Estrutura Molecular; Quinina/síntese química; Quinina/química; Quinina/farmacologia; Neoplasias Cutâneas/metabolismo; Neoplasias Cutâneas/patologia; Solubilidade; Relação Estrutura-Atividade

Palavras-chave

CTCL; HDAC inhibitors; Mycosis fungoides; Squaramide; Topical

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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Quinina / Neoplasias Cutâneas / Linfoma Cutâneo de Células T / Histona Desacetilase 1 / Histona Desacetilase 2 / Inibidores de Histona Desacetilases / Antineoplásicos Idioma: En Ano de publicação: 2018 Tipo de documento: Article

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