title: Binding of new aminopropan-2-ol compounds to bovine serum albumin, α1-acid glycoprotein and rat serum using equilibrium dialysis and LC/MS/MS.
abstract: BACKGROUND
  The binding of three new aminopropan-2-ol compounds briefly called 2F109, ANBL and TWo8 with potential cardiovascular activity to bovine serum albumin (BSA), α1-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 β- and α-adrenolytic mechanism of action. All analogues are weak bases with pKa values 8.65, 8.85 and 8.26 for 2F109, ANBL and TWo8, 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 μM, and 2.5 - 300 μM 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 (Kd for 2F109 = 8.49 x 10(-5) M, for ANBL= 1.92 x 10(-5) M, and for TWo8 = 1.71 x 10(-5) M) and low capacity (n = 0.53 for 2F109, 0.132 for ANBL and 0.13 for TWo8). The binding of 2F109, ANBL and TWo8 to AGP revealed one class of binding sites, with moderate affinity (Kd for 2F109 = 4.67 x 10(-6) M, for ANBL = 3.48 x 10(-5) M, and for TWo8 = 1.13 x 10(-5) M) and higher capacity (n = 2.21 for 2F109, 2.76 for ANBL and 2.28 for TWo8).
  
  
  CONCLUSIONS
  The obtained data indicate that 2F109, ANBL and TWo8 moderately bind to BSA (34.2 - 71.2%) with low capacity (Ka = 6.21 x 10(3) - 7.61 x 10(3)M(-1)) and strongly bind to AGP (71.5 - 85.5%) with moderate affinity (Ka = 7.94 x 10(4) - 4.73 x 10(5)M(-1)).
authors.affiliation: Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University, Medical College, Medyczna 9, PL 30-688 Kraków, Poland. maria.walczak@jcet.eu.
authors.forename: Maria
authors.initials: M
authors.lastname: Walczak
mesh_terms: D000818:Animals; D001665:Binding Sites; D002317:Cardiovascular Agents / Q000008:administration & dosage / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D003956:Dialysis; D007211:Indoles / Q000097:blood; D007275:Injections, Intravenous; D008297:Male; D009961:Orosomucoid / Q000378:metabolism*; D011412:Propanolamines / Q000008:administration & dosage / Q000097:blood*; D011485:Protein Binding; D051381:Rats; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000378:metabolism*; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry
chemical_list: C579251:1-(7-methoxy-1H-indol-4-yloxy)-3-(2-(2-methoxyphenoxy)ethylamino)propan-2-ol; D002317:Cardiovascular Agents; D007211:Indoles; D009961:Orosomucoid; D011412:Propanolamines; D012710:Serum Albumin, Bovine