Modulation of the spacer in N,N-bis(alkanol)amine aryl ester heterodimers led to the discovery of a series of highly potent P-glycoprotein-based multidrug resistance (MDR) modulators.

Dei, Silvia; Braconi, Laura; Trezza, Alfonso; Menicatti, Marta; Contino, Marialessandra; Coronnello, Marcella; Chiaramonte, Niccolò; Manetti, Dina; Perrone, Maria Grazia; Romanelli, Maria Novella; Udomtanakunchai, Chatchanok; Colabufo, Nicola Antonio; Bartolucci, Gianluca; Spiga, Ottavia; Salerno, Milena; Teodori, Elisabetta

Dei, Silvia; Braconi, Laura; Trezza, Alfonso; Menicatti, Marta; Contino, Marialessandra; Coronnello, Marcella; Chiaramonte, Niccolò; Manetti, Dina; Perrone, Maria Grazia; Romanelli, Maria Novella; Udomtanakunchai, Chatchanok; Colabufo, Nicola Antonio; Bartolucci, Gianluca; Spiga, Ottavia; Salerno, Milena; Teodori, Elisabetta.

Afiliação

Dei S; Department of Neuroscience, Psychology, Drug Research and Child's Health - Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, via Ugo Schiff 6, 50019 Sesto Fiorentino (FI), Italy. Electronic address: silvia.dei@unifi.it.
Braconi L; Department of Neuroscience, Psychology, Drug Research and Child's Health - Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, via Ugo Schiff 6, 50019 Sesto Fiorentino (FI), Italy.
Trezza A; Department of Biotechnology, Chemistry and Pharmacy, (Department of Excellence 2018-2022), University of Siena, via Aldo Moro 2, 53100 Siena, Italy.
Menicatti M; Department of Neuroscience, Psychology, Drug Research and Child's Health - Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, via Ugo Schiff 6, 50019 Sesto Fiorentino (FI), Italy.
Contino M; Department of Pharmacy - Drug Sciences, University of Bari Aldo Moro, via Orabona 4, 70125, Bari, Italy.
Coronnello M; Department of Health Sciences - Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139 Firenze, Italy.
Chiaramonte N; Department of Neuroscience, Psychology, Drug Research and Child's Health - Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, via Ugo Schiff 6, 50019 Sesto Fiorentino (FI), Italy.
Manetti D; Department of Neuroscience, Psychology, Drug Research and Child's Health - Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, via Ugo Schiff 6, 50019 Sesto Fiorentino (FI), Italy.
Perrone MG; Department of Pharmacy - Drug Sciences, University of Bari Aldo Moro, via Orabona 4, 70125, Bari, Italy.
Romanelli MN; Department of Neuroscience, Psychology, Drug Research and Child's Health - Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, via Ugo Schiff 6, 50019 Sesto Fiorentino (FI), Italy.
Udomtanakunchai C; Department of Radiologic Technology, Faculty of Associated Medical Sciences, Chang Mai University, 50200, Thailand.
Colabufo NA; Department of Pharmacy - Drug Sciences, University of Bari Aldo Moro, via Orabona 4, 70125, Bari, Italy.
Bartolucci G; Department of Neuroscience, Psychology, Drug Research and Child's Health - Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, via Ugo Schiff 6, 50019 Sesto Fiorentino (FI), Italy.
Spiga O; Department of Biotechnology, Chemistry and Pharmacy, (Department of Excellence 2018-2022), University of Siena, via Aldo Moro 2, 53100 Siena, Italy.
Salerno M; University of Paris 13, Sorbonne Paris Cité, Laboratoire CSPBAT, CNRS (UMR 7244), UFR-SMBH, 74 rue Marcel Cachin, 93017 Bobigny, France.
Teodori E; Department of Neuroscience, Psychology, Drug Research and Child's Health - Section of Pharmaceutical and Nutraceutical Sciences, University of Florence, via Ugo Schiff 6, 50019 Sesto Fiorentino (FI), Italy.

Eur J Med Chem ; 172: 71-94, 2019 Jun 15.

Article em En | MEDLINE | ID: mdl-30947123

Assuntos

Membro 1 da Subfamília B de Cassetes de Ligação de ATP/antagonistas & inibidores; Aminas/farmacologia; Antineoplásicos/farmacologia; Resistência a Múltiplos Medicamentos/efeitos dos fármacos; Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos; Ésteres/farmacologia; Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/antagonistas & inibidores; Membro 2 da Subfamília G de Transportadores de Cassetes de Ligação de ATP/metabolismo; Aminas/síntese química; Aminas/química; Antineoplásicos/síntese química; Antineoplásicos/química; Células CACO-2; Dimerização; Relação Dose-Resposta a Droga; Ésteres/síntese química; Ésteres/química; Humanos; Células K562; Modelos Moleculares; Estrutura Molecular; Proteínas Associadas à Resistência a Múltiplos Medicamentos/antagonistas & inibidores; Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo; Proteínas de Neoplasias/antagonistas & inibidores; Proteínas de Neoplasias/metabolismo; Relação Estrutura-Atividade; Células Tumorais Cultivadas

Palavras-chave

1-(3-dimethylaminopropyl)-3-ethylcarbodiimmide hydrochloride; 4-Dimethylaminopyridine; ATPase activity; Apparent permeability; BCRP; BCRP modulators; Breast cancer resistance protein; Caco-2â¯cells; Colorectal adenocarcinoma cells; DMAP; DOX; Doxorubicin; EDCI; Human plasma stability; KEE; Ketoprofen Ethyl Ester; MDCK; MDR reversers; MRP1; MRP1 modulators; Madin-Darby Canin Kidney; Molecular docking; Multidrug resistance associated protein 1; P-glycoprotein; P-gp; P-gp modulators; PBS; PDB; Phosphate buffer solution; Pirarubicin uptake; Protein data bank; Rhd123; Rhodamine-123; Rhodamine-123 efflux; TPSA; Topological polar surface area

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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Membro 1 da Subfamília B de Cassetes de Ligação de ATP / Resistência a Múltiplos Medicamentos / Resistencia a Medicamentos Antineoplásicos / Ésteres / Aminas / Antineoplásicos Limite: Humans Idioma: En Ano de publicação: 2019 Tipo de documento: Article

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