PT  - JOURNAL ARTICLE
AU  - Chiba, P
AU  - Ecker, G
AU  - Schmid, D
AU  - Drach, J
AU  - Tell, B
AU  - Goldenberg, S
AU  - Gekeler, V
TI  - Structural requirements for activity of propafenone-type modulators in P-glycoprotein-mediated multidrug resistance.
DP  - 1996 Jun 01
TA  - Molecular Pharmacology
PG  - 1122--1130
VI  - 49
IP  - 6
4099  - http://molpharm.aspetjournals.org/content/49/6/1122.short
4100  - http://molpharm.aspetjournals.org/content/49/6/1122.full
SO  - Mol Pharmacol1996 Jun 01; 49
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.