Chiba P, Ecker G, Schmid D, Drach J, Tell B, Goldenberg S, Gekeler V
Department of Medical Chemistry, University of Vienna, Austria.
Mol Pharmacol. 1996 Jun;49(6):1122-30.
The sodium channel blocker propafenone and a series of analogs have been identified as effective modulators of P-glyco-protein-mediated multidrug resistance in human tumor cells. A series of closely related structural homologues showed a highly significant correlation between lipophilicity and pharmacological effect. Reduction of the carbonyl group as well as conversion to a methylether led to a remarkable decrease in activity, whereby lipophilicity lost its predictive character as the main determinant for modulator potency. Similarly, the relative positioning of the acyl- and propanolamine side chains also influences activity, so the distance between carbonyl group and nitrogen atom seems important.
