Binding of new aminopropan-2-ol compounds to bovine serum albumin,ai-acid glycoprotein and rat serum using equilibrium dialysis and LC/MS/MS

Background: the binding of three new aminopropan-2-ol compounds briefly called 2f109,anbl and tw08 with potential cardiovascular activity to bovine serum albumin (bsa),ai-acid glycoprotein (agp) and to rat serum was studied. the chemical structures of these compounds are related to carvedilol. they possess an antiarrhythmic and hypotensive activity,and p- and a-adrenolytic mechanism of action. all analogues are weak bases with pka values 8.65,8.85 and 8.26 for 2f109,anbl and tw08,respectively,and they possess lipophilic character (log p > 1.9584). methods: the extent of protein binding was determined using equilibrium dialysis in the range 2.5 - 900 um,and 2.5 - 300 um for binding of investigated compounds to bsa and agp,respectively,and the quantitative measurement was done by lc/esi-ms/ms assay. results: the studied compounds bound to a single class of binding sites on bsa which was characterized by low affinity (kj for 2f109 = 8.49x 105m,for anbl = 1.92 x 105 m,and for two8 = 1.71 x 1(t5m) and low capacity (n = 0.53 for 2f109,0.132 for anbl and 0.13 for tw08). the binding of 2f109,anbl and tw08 to agp revealed one class of binding sites,with moderate affinity (kd for 2f109 = 4.67 x 106 m,for anbl = 3.48 x qr5 m,and for tw08 = 1.13 x 105 m) and higher capacity (n = 2.21 for 2f109,2.76 for anbl and 2.28 for tw08). conclusion: the obtained data indicate that 2f109,anbl and tw08 moderately bind to bsa (34.2 - 71.2%) with low capacity (ka = 6.21 x 103-7.61 x 103m-1)andstronglybindtoagp(71.5-85.5%) withmoderateaffinity(ka = 7.94x 104-4.73x.copyright © 2013 by institute of pharmacology polish academy of sciences.