Studying The Non-covalent Binding Interactions Between Strychnine, Brucine And Human Serum Albumin

Parts of the drugs will combine with the protein in the blood after they absorded, this combination may affect the drugs' activity. Study on the interactions between drug and protein can help people to understand the distribution, mechanism and toxic of the drug. Brucine and strychnine are the main compositions of alkaloid in nux vomica. A lot of researches showed that strychnine and brucine have a wide of pharmacological activities, but they also have considerable toxic. Strychnine and brucine belong to the drugs of narrow therapeutic window, litter change on the concentration may cause the poison. Therefore, this study reaserched the interactions between the two drugs and plasma proteins.Some related parameters were given, and these parameters may provide some guidance for the clinical dose. Among all methods for studying the interactions, the fluorescence technique is widely used because of its high sensitivity, rapidity and ease of implementation, the equilibrium dialysis is also a classic method to determinate the concentration of drugs for its easy and economical. In this dissertation, fluorescence quenching and equilibrium dialysis are used to investigate the interactions of strychnine and brucine and human serum albumin(HSA) for the first time. the main results are as follows:(1) When the temperature were 25℃and 35℃, the binding constant Ka between brucine and HSA were 2.12×104 mol/L and 1.97×104 mol/L, respectively. The binding sites value (n) were 1.07 and 1.07, while, the binding constant K2 for strychnine and HSA were 6.34×103 mol/L and 3.05×103 mol/L. The binding sites value (n) were 1.01 and 0.97. The main binding force are hydrogen bond and vander waals force.(2) In the condition of 37℃, the protein binding rate of the strychnine and brucine are about 40% and 16% respectively. Using scatchard method to deal with the result, the Ka between strychnine and brucine and HSA are 2.7111×104 and 9.7738×103 L/mol while, the binding sites value (n) are 0.84 and 0.67, respectively. All the above results will provide a guidance for clinical dose of the two drugs.