Analysis of the molecular interactions and complexation of chloroquine with bovine serum albumin

Abstract

Pharmacokinetic parameters, drug bioavailability, and biological activities depend on the mechanisms of interaction with serum albumin. In this study, the binding properties as well as mechanisms of interaction of chloroquine with bovine serum albumin (BSA) were investigated. The binding of chloroquine with BSA was carried out using a microcalorimetric approach. The mechanism of binding, the number of binding molecules as well as changes of BSA upon complexation with chloroquine were investigated. The binding isotherms indicated a variable number of binding sites of chloroquine on one molecule of BSA. At lower temperatures, larger numbers of binding sites were available for chloroquine, these decrease by increasing the temperature. The binding constant of chloroquine with BSA varied from 9.4×10³ M⁻¹ at 25°C to 5.7×10³ M⁻¹ at 40°C. Chloroquine showed temperature-dependent binding affinity, with stronger affinity at lower temperature. By increasing the temperature, from 25°C to 40°C, the binding affinity was decreased by approximately 60% of its value. Chloroquine showed weak binding affinity with BSA. The weak binding affinity of chloroquine with BSA is important in determining the drug-drug interactions at the binding sites of BSA. The presence of stronger binding ligands, e.g., chloramphenicol, tetracyclines or diclofenac, can compete with chloroquine for its binding sites, and therefore lowers its serum albumin binding. This study will be helpful in understanding the binding properties of mechanisms of interaction of chloroquine with BSA.