1024592-65-1Relevant academic research and scientific papers
6,7-Dimethoxy-2-phenethyl-1,2,3,4-tetrahydroisoquinoline amides and corresponding ester isosteres as multidrug resistance reversers
Bartolucci, Gianluca,Braconi, Laura,Colabufo, Nicola Antonio,Contino, Marialessandra,Dei, Silvia,Giampietro, Roberta,Manetti, Dina,Perrone, Maria Grazia,Riganti, Chiara,Romanelli, Maria Novella,Teodori, Elisabetta,Chiaramonte, Niccolò
, p. 974 - 992 (2020)
Aiming to deepen the structure–activity relationships of the two P-glycoprotein (P-gp) modulators elacridar and tariquidar, a new series of amide and ester derivatives carrying a 6,7-dimethoxy-2-phenethyl-1,2,3,4-tetrahydroisoquinoline scaffold linked to different methoxy-substituted aryl moieties were synthesised. The obtained compounds were evaluated for their P-gp interaction profile and selectivity towards the two other ABC transporters, multidrug-resistance-associated protein-1 and breast cancer resistance protein, showing to be very active and selective versus P-gp. Two amide derivatives, displaying the best P-gp activity, were tested in co-administration with the antineoplastic drug doxorubicin in different cancer cell lines, showing a significant sensitising activity towards doxorubicin. The investigation on the chemical stability of the derivatives towards spontaneous or enzymatic hydrolysis, showed that amides are stable in both models while some ester compounds were hydrolysed in human plasma. This study allowed us to identify two chemosensitizers that behave as non-transported substrates and are characterised by different selectivity profiles.
Synthesis and biological evaluation of a small molecule library of 3rd generation multidrug resistance modulators
Klinkhammer, Werner,Mueller, Henrik,Globisch, Christoph,Pajeva, Ilza K.,Wiese, Michael
experimental part, p. 2524 - 2535 (2009/09/05)
The development of new modulators possessing high efficacy, low toxicity and high selectivity is a pivotal approach to overcoming P-glycoprotein (P-gp) mediated multidrug resistance (MDR) in tumour cells. In this study 39 compounds are presented which hav
