Serum albumin binds several drugs making reversible bonds and the degree of the interaction is relevant to tissues drug distribution and, consequently, to either it?s pharmacological or toxic effectiveness.
Serum albumin binds selectively hydrophobic ligands such as drugs and medicines, therefore, hydrofobicity as well as chemical groups, can be an indicator of the strength of the interaction they make.
Tetracycline (TC) is a broad-spectrum antibiotic and its stability can be affected by diverse factors such as temperature, pH and light. The main degradation product in acid solution is Anhydroustetracycline (AHTC) which is highly toxic to mammals.
In the present work we have measured the relative hydrofobicity of both drugs by the application of electrochemical techniques to an interface formed by two non miscible solutions of electrolytes. We determined the partition constants (Kd) for the water/1,2-dichloroethane interface and they revealed that AHTC is considerably more hydrofobic than TC. As we consider hydrofobicity as the main factor in the preferential interaction with serum albumin, we predicted that AHTC interacts with higher affinity than TC does. These results were correlated with experiments of differential scanning calorimetry (DSC). The calorimetric profiles of bovine serum albumin were obtained in absence and presence of TC and AHTC. We observed that AHTC enhances the thermal stability of BSA significantly more than TC does at the same ligand:protein mole ratio; AHTC increases the temperature of midpoint denaturation (Tm) 7ºC while TC does not produce any significant change in this parameter.
Finally, we obtained the number of binding sites and we estimated a value of binding constant (Kb) of AHTC to BSA from calorimetric data of denaturation of BSA at different concentrations of AHTC. These results were compared with those obtained with other techniques.
