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, 16, 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.

Multidrug resistance (MDR) reversers: High activity and efficacy in a series of asymmetrical N,N-bis(alkanol)amine aryl esters / Silvia Dei; Marcella Coronnello; Elisa Floriddia; Gianluca Bartolucci; Cristina Bellucci; Luca Guandalini; Dina Manetti; Maria Novella Romanelli; Milena Salerno; Ivan Bello; Enrico Mini; Elisabetta Teodori. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - STAMPA. - 87:(2014), pp. 398-412. [10.1016/j.ejmech.2014.09.084]

Multidrug resistance (MDR) reversers: High activity and efficacy in a series of asymmetrical N,N-bis(alkanol)amine aryl esters

DEI, SILVIA;CORONNELLO, MARCELLA MARIA;FLORIDDIA, ELISA;BARTOLUCCI, GIAN LUCA;BELLUCCI, CRISTINA;GUANDALINI, LUCA;MANETTI, DINA;ROMANELLI, MARIA NOVELLA;MINI, ENRICO;TEODORI, ELISABETTA
2014

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, 16, 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.
2014
87
398
412
Silvia Dei; Marcella Coronnello; Elisa Floriddia; Gianluca Bartolucci; Cristina Bellucci; Luca Guandalini; Dina Manetti; Maria Novella Romanelli; Milena Salerno; Ivan Bello; Enrico Mini; Elisabetta Teodori
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/919930
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