1208863-39-1Relevant articles and documents
Structure-activity relationships studies in a series of N,N-bis(alkanol)amine aryl esters as P-glycoprotein (Pgp) dependent multidrug resistance (MDR) inhibitors
Martelli, Cecilia,Coronnello, Marcella,Dei, Silvia,Manetti, Dina,Orlandi, Francesca,Scapecchi, Serena,Romanelli, Maria Novella,Salerno, Milena,Mini, Enrico,Teodori, Elisabetta
experimental part, p. 1755 - 1762 (2010/08/06)
As a continuation of a previous research, a series of N,N-bis(alkanol)amine aryl esters, as Pgpdependent MDR inhibitors, was designed and synthesized. The aromatic ester portions are suitably modulated, and new aryl rings (Ar 1 and Ar2) were combined with trans-3-(3,4,5- trimethoxyphenyl)vinyl, 3,4,5-trimethoxybenzyl and anthracene moieties that were present in the most potent previously studied compounds. The new compounds showed a wide range of potencies and efficacies on doxorubicin-resistant erythroleukemia K562 cells (K562/DOX) in the pirarubicin uptake assay. Selected compounds (5, 6, 8, 9, and 21) were further studied, evaluating their action on doxorubicin cytotoxicity potentiation on K562 cells; they significantly enhanced doxorubicin cytotoxicity on K562/DOX cells, confirming the results obtained with pirarubicin. Compound, 9 shows the most promising properties as it was able to nearly completely reverse Pgp-dependent pirarubicin extrusion at nanomolar doses and increased the cytotoxicity of doxorubicin with a reversal fold (RF) of 19.1. at 3 μM dose.
