Premium
A Combined Hansch/Free‐Wilson Approach as Predictive Tool in QSAR Studies on Propafenone‐Type Modulators of Multidrug Resistance
Author(s) -
Tmej Claudia,
Chiba Peter,
Huber Mario,
Richter Elisabeth,
Hitzler Manuela,
Schaper KlausJürgen,
Ecker Gerhard
Publication year - 1998
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/(sici)1521-4184(199807)331:7/8<233::aid-ardp233>3.0.co;2-2
Subject(s) - chemistry , quantitative structure–activity relationship , propafenone , potency , molar refractivity , stereochemistry , multiple drug resistance , pharmacology , in vitro , combinatorial chemistry , biochemistry , medicine , biology , antibiotics , atrial fibrillation
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 ( Q 2 cv = 0.66). The combined approach results in equations with remarkably higher predictive power ( Q 2 cv = 0.83), specifically molar refractivity shows high significance in all equations derived. This indicates that polar interactions also contribute to protein binding.