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

作者：Dei Silvia^*; Coronnello Marcella; Floriddia Elisa; Bartolucci Gianluca; Bellucci Cristina; Guandalini Luca; Manetti Dina; Romanelli Maria Novella; Salerno Milena; Bello Ivan; Mini Enrico; Teodori Elisabetta

来源：European Journal of Medicinal Chemistry, 2014, 87: 398-412.

DOI：10.1016/j.ejmech.2014.09.084

• MDR reversers
• P-gp inhibitors
• N,N-bis(alkanol)amine aryl esters
• Chemosensitizers
• Doxorubicin-resistant erythroleukemia
• K562 cells (K562/DOX)
• Pirarubicin uptake

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.

• 出版日期2014-11-24