A combined Hansch/Free-Wilson approach as predictive tool in QSAR studies on propafenone-type modulators of multidrug resistance.

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Tmej C, Chiba P, Huber M, Richter E, Hitzler M, Schaper KJ, Ecker G

A combined Hansch/Free-Wilson approach as predictive tool in QSAR studies on propafenone-type modulators of multidrug resistance.

Arch Pharm (Weinheim). 1998 Jul-Aug;331(7-8):233-40.

PubMed ID

9747179 [ View in PubMed

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Abstract

A series of 48 propafenone-type modulators of multidrug resistance was synthesized and their P-glycoprotein inhibitory activity was measured using the daunomycin efflux assay. Both a Free-Wilson and a combined Hansch/Free-Wilson analysis were performed using log P, partial log P and molar refraction values as Hansch descriptors. The results of the Free-Wilson analysis show that modifications on the central aromatic ring generally influence pharmacological activity, whereby in almost all cases a decrease in MDR-modulating potency is observed (Q2cv = 0.66). The combined approach results in equations with remarkably higher predictive power (Q2cv = 0.83), specifically molar refractivity shows high significance in all equations derived. This indicates that polar interactions also contribute to protein binding.

DrugBank Data that Cites this Article

Drug Transporters

Drug	Transporter	Kind	Organism	Pharmacological Action	Actions
Propafenone	P-glycoprotein 1	Protein	Humans	Unknown	Inhibitor	Details