title: Diphenylcyclohexylamine derivatives as new potent multidrug resistance (MDR) modulators.
abstract: A series of compounds with a diphenylmethyl cyclohexyl skeleton, loosely related to verapamil, has been synthesized and tested as MDR modulators on anthracycline-resistant erythroleukemia K 562 cells. Their residual cardiovascular action (negative inotropic and chronotropic activity as well as vasorelaxant activity) was evaluated on guinea-pig isolated atria preparations and on guinea-pig aortic strip preparations. Most compounds of the series possess a good MDR-reverting activity together with a low cardiovascular action. Among them, compounds 3a1, 7a, and 8a are more potent than verapamil as MDR reverters and lack any cardiovascular action; they can represent useful leads for the development of new safe MDR reversing drugs.
authors.affiliation: Dipartimento di Scienze Farmaceutiche, Università di Firenze, via U. Schiff 6, 50019 Sesto Fiorentino (FI), Italy. silvia.dei@unifi.it
authors.forename: Silvia
authors.initials: S
authors.lastname: Dei
authors.forename: Roberta
authors.initials: R
authors.lastname: Budriesi
authors.forename: Paiwan
authors.initials: P
authors.lastname: Sudwan
authors.forename: Marta
authors.initials: M
authors.lastname: Ferraroni
authors.forename: Alberto
authors.initials: A
authors.lastname: Chiarini
authors.forename: Arlette
authors.initials: A
authors.lastname: Garnier-Suillerot
authors.forename: Dina
authors.initials: D
authors.lastname: Manetti
authors.forename: Cecilia
authors.initials: C
authors.lastname: Martelli
authors.forename: Serena
authors.initials: S
authors.lastname: Scapecchi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Teodori
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D003514:Cyclohexylamines / Q000737:chemistry / Q000494:pharmacology*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D020014:K562 Cells; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry
chemical_list: D003514:Cyclohexylamines