In vitro study on the interaction of mechanism of tricyclic compounds with bovine serum albumin

The mechanism of interaction of five phenothiazine drugs with bovine serum albumin has been investigated using fluorescence spectroscopy, circular dichroism and equilibrium dialysis methods. It was found that the phenothiazine ring common to all drugs makes major contribution to interaction. However, the nature of alkylamino group at position 10 influences the protein binding significantly. Binding affinities could be related to parachor values of drugs. Stern-Volmer plots indicated the presence of static component in the quenching mechanism. Results also showed that both tryptophan residues of protein are accessible to drug molecules. The high magnitude of rate constant of quenching indicated that the process of energy transfer occurs by intermolecular interaction forces and thus drug-binding site is in close proximity to tryptophan residues of BSA. Binding studies in presence of hydrophobic probe, 8-anilino-1-naphthalein-sulphonic acid showed that there is hydrophobic interaction between drugs and the probe and they do not share common sites in BSA. Fluorescence intensity data in the presence of additives showed that hydrophobic interactions play a significant role. Small decrease in critical micellar concentration of anionic surfactant, sodium dodecyl sulfate in the presence of drugs showed that the ionic character of drugs also contribute to binding. Thermodynamic parameters obtained from data at different temperatures showed that the binding of phenothiazine drugs to BSA involve hydrophobic bonds predominantly. The CD spectrum of BSA in presence of drugs shows that binding of drugs leads to change in the helicity of the protein. The binding of these drugs to BSA based on dialysis experiment has been characterized by association constant (K) and the number of binding sites (n). (C) 2004 Elsevier B.V. All rights reserved.