RT Journal Article
SR Electronic
T1 Structural requirements for activity of propafenone-type modulators in P-glycoprotein-mediated multidrug resistance.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 1122
OP 1130
VO 49
IS 6
A1 Chiba, P
A1 Ecker, G
A1 Schmid, D
A1 Drach, J
A1 Tell, B
A1 Goldenberg, S
A1 Gekeler, V
YR 1996
UL http://molpharm.aspetjournals.org/content/49/6/1122.abstract
AB 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.