1233224-70-8Relevant articles and documents
Progesterone-adenine hybrids as bivalent inhibitors of P-glycoprotein- mediated multidrug efflux: Design, synthesis, characterization and biological evaluation
Zeinyeh, Wael,Mahiout, Zahia,Radix, Sylvie,Lomberget, Thierry,Dumoulin, Axel,Barret, Roland,Grenot, Catherine,Rocheblave, Luc,Walchshofer, Nadia,Matera, Eva-Laure,Dumontet, Charles
, p. 1177 - 1191,15 (2020/08/20)
Bivalent ligands were designed on the basis of the described close proximity of the ATP-site and the putative steroid-binding site of P-glycoprotein (ABCB1). The syntheses of 19 progesterone-adenine hybrids are described. Their abilities to inhibit P-glycoprotein-mediated daunorubicin efflux in K562/R7 human leukemic cells overexpressing P-glycoprotein were evaluated versus progesterone. The hybrid with a hexamethylene linker chain showed the best inhibitory potency. The efficiency of these progesterone-adenine hybrids depends on two main factors: (i) the nature of the linker and (ii) its attachment point on the steroid skeleton.