title: Design, synthesis and evaluation of progesterone-adenine hybrids as bivalent inhibitors of P-glycoprotein-mediated multidrug efflux.
abstract: Steroidal bivalent ligands were designed on the basis of the described closer proximity of the ATP-site and the putative steroid-binding site of P-glycoprotein (ABCB1). The syntheses of seven progesterone-adenine hybrids were described. Their abilities to inhibit P-glycoprotein-mediated daunorubicin efflux in K562/R7 human leukemic cells overexpressing P-glycoprotein were evaluated versus progesterone.
authors.affiliation: Université de Lyon, Université Lyon 1, ISPB-Faculté de Pharmacie, INSERM U863, F-69373 Lyon cedex 08, France.
authors.forename: Waël
authors.initials: W
authors.lastname: Zeinyeh
authors.forename: Ghina
authors.initials: G
authors.lastname: Alameh
authors.forename: Sylvie
authors.initials: S
authors.lastname: Radix
authors.forename: Catherine
authors.initials: C
authors.lastname: Grenot
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
authors.forename: Nadia
authors.initials: N
authors.lastname: Walchshofer
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000225:Adenine / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D045744:Cell Line, Tumor; D003630:Daunorubicin / Q000494:pharmacology; D015195:Drug Design; D006801:Humans; D011374:Progesterone / Q000737:chemistry*
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D011374:Progesterone; D000225:Adenine; D003630:Daunorubicin