title: Multidrug resistance (MDR) reversers: High activity and efficacy in a series of asymmetrical N,N-bis(alkanol)amine aryl esters.
abstract: As a continuation of our research on potent and efficacious P-gp-dependent multidrug resistance (MDR) reversers, several new N,N-bis(alkanol)amine aryl esters were designed and synthesized, varying the aromatic moieties or the length of the methylenic chain. The new compounds were tested on doxorubicin-resistant erythroleukemia K562 cells (K562/DOX) in the pirarubicin uptake assay, where most of the new compounds were shown to be active. In particular the asymmetrical compounds, characterized by two linkers of different length, generally showed fairly high activities as MDR reversers. Some selected compounds (isomers 15-17) were further studied by evaluating their doxorubicin cytotoxicity enhancement (reversal fold, RF) on the K562/DOX cell line. The results of both pharmacological assays indicate that compounds 16 (GDE6) and 17 (GDE19) could be interesting leads for the development of new P-gp dependent MDR modulators.
authors.affiliation: Dipartimento NEUROFARBA-Sezione di Farmaceutica e Nutraceutica, Università di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, FI, Italy. Electronic address: silvia.dei@unifi.it.
authors.forename: Silvia
authors.initials: S
authors.lastname: Dei
authors.affiliation: Dipartimento di Scienze della Salute, Università di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Coronnello
authors.affiliation: Dipartimento NEUROFARBA-Sezione di Farmaceutica e Nutraceutica, Università di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, FI, Italy.
authors.forename: Elisa
authors.initials: E
authors.lastname: Floriddia
authors.affiliation: Dipartimento NEUROFARBA-Sezione di Farmaceutica e Nutraceutica, Università di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, FI, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Bartolucci
authors.affiliation: Dipartimento NEUROFARBA-Sezione di Farmaceutica e Nutraceutica, Università di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, FI, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bellucci
authors.affiliation: Dipartimento NEUROFARBA-Sezione di Farmaceutica e Nutraceutica, Università di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, FI, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Guandalini
authors.affiliation: Dipartimento NEUROFARBA-Sezione di Farmaceutica e Nutraceutica, Università di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, FI, Italy.
authors.forename: Dina
authors.initials: D
authors.lastname: Manetti
authors.affiliation: Dipartimento NEUROFARBA-Sezione di Farmaceutica e Nutraceutica, Università di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, FI, Italy.
authors.forename: Maria Novella
authors.initials: MN
authors.lastname: Romanelli
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, Laboratoire CSPBAT, CNRS (UMR 7244), UFR-SMBH, 74 Rue Marcel Cachin, 93017 Bobigny, France.
authors.forename: Milena
authors.initials: M
authors.lastname: Salerno
authors.affiliation: Université Paris 13, Sorbonne Paris Cité, Laboratoire CSPBAT, CNRS (UMR 7244), UFR-SMBH, 74 Rue Marcel Cachin, 93017 Bobigny, France.
authors.forename: Ivan
authors.initials: I
authors.lastname: Bello
authors.affiliation: Dipartimento di Scienze della Salute, Università di Firenze, Viale Pieraccini 6, 50139 Firenze, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Mini
authors.affiliation: Dipartimento NEUROFARBA-Sezione di Farmaceutica e Nutraceutica, Università di Firenze, Via Ugo Schiff 6, 50019 Sesto Fiorentino, FI, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Teodori
mesh_terms: D000588:Amines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000378:metabolism; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004952:Esters; D006801:Humans; D007536:Isomerism; D020014:K562 Cells
chemical_list: D000588:Amines; D000970:Antineoplastic Agents; D004952:Esters; D004317:Doxorubicin; C027260:pirarubicin
keywords: Chemosensitizers; Doxorubicin-resistant erythroleukemia K562 cells (K562/DOX); MDR reversers; N,N-bis(alkanol)amine aryl esters; P-gp inhibitors; Pirarubicin uptake