Tocainide analogues binding to human serum albumin: a HPLAC and circular dichroism study.

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Pistolozzi M, Franchini C, Corbo F, Muraglia M, De Giorgi M, Felix G, Bertucci C

Tocainide analogues binding to human serum albumin: a HPLAC and circular dichroism study.

J Pharm Biomed Anal. 2010 Oct 10;53(2):179-85. doi: 10.1016/j.jpba.2010.03.005. Epub 2010 Mar 7.

PubMed ID

20359840 [ View in PubMed

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Abstract

A series of synthesised tocainide analogues were characterized for their human serum albumin (HSA) binding, using high-performance liquid affinity chromatography (HPLAC) and circular dichroism (CD). The synthesis and physico-chemical characterization of compounds 7a-7d is reported here. For the HPLAC investigation HSA was covalently immobilized to the silica matrix of the HPLC column, using an anchoring procedure, which allows the binding properties of the protein to be maintained. The HSA-based column was used for getting information on the high affinity binding sites of the tocainide analogues to HSA. According to the displacement chromatography approach, the retentions of the analytes were determined in the absence and in the presence of increasing concentrations of competitors known to bind to specific binding sites on the protein. The same system, drug/protein, was investigated in solution by CD. The analysed compounds, proved active as sodium channel blockers, showed a much higher affinity to the serum carrier with respect to the parent compound, tocainide. Further, a non-cooperative interaction at sites I and II, and an almost independent binding at the bilirubin binding site on HSA were hypothesised on the bases of the competition experiments.

DrugBank Data that Cites this Article

Drug Carriers

Drug	Carrier	Kind	Organism	Pharmacological Action	Actions
Tocainide	Serum albumin	Protein	Humans	No	Other/unknown	Details