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Chiba, P. et al.

Chiba, Ecker, Schmid, Drach, Tell, Goldenberg, Gekeler,

Structural requirements for activity of propafenone-type modulators in P-glycoprotein- mediated multidrug resistance.

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.[1]

References

Structural requirements for activity of propafenone-type modulators in P-glycoprotein-mediated multidrug resistance. Chiba, P., Ecker, G., Schmid, D., Drach, J., Tell, B., Goldenberg, S., Gekeler, V. Mol. Pharmacol. (1996) [Pubmed]

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