Diphenylcyclohexylamine derivatives as new potent multidrug resistance (MDR) modulators.
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.
Dei
Silvia
S
Dipartimento di Scienze Farmaceutiche, Università di Firenze, via U. Schiff 6, 50019 Sesto Fiorentino (FI), Italy. silvia.dei@unifi.it
Budriesi
Roberta
R
Sudwan
Paiwan
P
Ferraroni
Marta
M
Chiarini
Alberto
A
Garnier-Suillerot
Arlette
A
Manetti
Dina
D
Martelli
Cecilia
C
Scapecchi
Serena
S
Teodori
Elisabetta
E
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
D003514:Cyclohexylamines