Ca2 binding and translocating properties of diflunisal

AbstractWe have characterized the binding of Ca2+ and Mg2+ to the anti‐inflammatory drug diflunisal in acetonitrile and demonstrated the drug‐mediated transport of Ca2+ across the lipid bilayer in unilamellar vesicles made of 1,2‐dimyristoyl‐sn‐glycero‐3‐phosphocholine. Fluorescence and difference absorption spectral data show that diflunisal undergoes a significant conformational change on binding Ca2+ and Mg2+ forming, respectively, 1:2 and 1:1 cation:drug complexes with Kd in the low µM range. The kinetics of transport showed that Ca2+ was transported into the vesicle as 1:2 Ca2+:diflunisal sandwich complex. This suggests that the interaction of the drug with the cation in the lipid and the lipid‐mimetic solvent are similar. The biological relevance of the Ca2+‐binding and translocating abilities of diflunisal is examined in light of the reported ionophoretic properties of several phospholipids as well as cyclooxygenase and lipoxygenase products.

Ca2 binding and translocating properties of diflunisal Journal Articles