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Binding of new aminopropan-2-ol compounds to bovine serum albumin, α1-acid glycoprotein and rat serum using equilibrium dialysis and LC/MS/MS

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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 (Kj for 2F109 = 8.49 × 10-5 M, for ANBL = 1.92 × 10-5 M, and for TWo8 = 1.71 × 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 × 10-6 M, for ANBL = 3.48 × 10-5 M, and for TWo8 = 1.13 × 10-5 M) and higher capacity (n = 2.21 for 2F109, 2.76 for ANBL and 2.28 for TW68).

Conclusion

The obtained data indicate that 2F109, ANBL and TWo8 moderately bind to BSA (34.2–71.2%) with low capacity (Ka = 6.21 × 10-3–7.61 × 103M-1) and strongly bind to AGP (71.5–85.5%)with moderate affinity (Ka = 7.94 × 104–4.73 × 105M-1).

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Authors and Affiliations

  1. Department of Pharmacokinetics and Physical Pharmacy, Jagiellonian University, Medical College, Medyczna 9, PL 30-688, Kraków, Poland

    Maria Walczak

  2. Jagiellonian Centre for Experimental Therapeutics, Jagiellonian University, Bobrzyńskiego 14, PL 30-348, Kraków, Poland

    Maria Walczak

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Correspondence to Maria Walczak.

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Walczak, M. Binding of new aminopropan-2-ol compounds to bovine serum albumin, α1-acid glycoprotein and rat serum using equilibrium dialysis and LC/MS/MS. Pharmacol. Rep 65, 1294–1303 (2013). https://doi.org/10.1016/S1734-1140(13)71487-7

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  • DOI: https://doi.org/10.1016/S1734-1140(13)71487-7

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