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.
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.
Teodori
Elisabetta
E
Dipartimento di Scienze Farmaceutiche, Università di Firenze, via U. Schiff 6, 50019 Sesto Fiorentino (FI), Italy.
Martelli
Cecilia
C
Salerno
Milena
M
Darghal
Nacira
N
Dei
Silvia
S
Garnier-Suillerot
Arlette
A
Gualtieri
Fulvio
F
Manetti
Dina
D
Scapecchi
Serena
S
Romanelli
Maria Novella
MN
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
D018435:ATP Binding Cassette Transporter, Subfamily B; D000970:Antineoplastic Agents; D003511:Cyclohexanols; D004952:Esters; D004317:Doxorubicin; C027260:pirarubicin