title: Isomeric N,N-bis(cyclohexanol)amine aryl esters: the discovery of a new class of highly potent P-glycoprotein (Pgp)-dependent multidrug resistance (MDR) inhibitors.
abstract: A new series of P-glycoprotein (Pgp)-dependent multidrug resistance (MDR) inhibitors having a N,N-bis(cyclohexanol)amine scaffold have been designed, following the frozen analog approach. With respect to the parent flexible molecules, the new compounds show improved potency and efficacy. Among them, compound 1d, on anthracycline-resistant erythroleukemia K562 cells, is able to completely reverse Pgp-dependent MDR at low nanomolar concentration.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Firenze, via U. Schiff 6, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Teodori
authors.forename: Cecilia
authors.initials: C
authors.lastname: Martelli
authors.forename: Milena
authors.initials: M
authors.lastname: Salerno
authors.forename: Nacira
authors.initials: N
authors.lastname: Darghal
authors.forename: Silvia
authors.initials: S
authors.lastname: Dei
authors.forename: Arlette
authors.initials: A
authors.lastname: Garnier-Suillerot
authors.forename: Fulvio
authors.initials: F
authors.lastname: Gualtieri
authors.forename: Dina
authors.initials: D
authors.lastname: Manetti
authors.forename: Serena
authors.initials: S
authors.lastname: Scapecchi
authors.forename: Maria Novella
authors.initials: MN
authors.lastname: Romanelli
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000502:physiology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D003511:Cyclohexanols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004317:Doxorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004952:Esters; D006801:Humans; D013237:Stereoisomerism
chemical_list: D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D003511:Cyclohexanols; D004952:Esters; D004317:Doxorubicin; C027260:pirarubicin