Related Experiment Video
Updated: May 12, 2026
A Rapid and Quantitative Fluorimetric Method for Protein-Targeting Small Molecule Drug Screening
Published on: October 16, 2015
Fluorescence spectroscopic study for competitive binding of antidiabetic drugs and endogenous substances on serum
Neelam Seedher1, Mamta Kanojia
1Department of Chemistry, Panjab University, Chandigarh 160014, India. nseedher@yahoo.com
Background:
The hypoglycemic effect of antidiabetic drugs varies with change in the level of endogenous substances in the body in diseased states largely due to alteration in drug-serum albumin binding affinity. The aim of the present study was to understand and quantify this effect.
Methods:
Quenching of intrinsic fluorescence of human serum albumin was used to monitor the competitive binding of antidiabetic drugs (gliclazide, glimepiride, glipizide and repaglinide) and bilirubin/hemin/chloride ions.
Results And Conclusions:
Bilirubin and hemin were bound at site I and site II in human serum albumin with association constants of the order of 105. The presence of bilirubin decreased the binding affinity of all the antidiabetic drugs. In the presence of hemin, the binding of gliclazide and glimepiride increased significantly, whereas that of glipizide and repaglinide decreased. The presence of chloride ions decreased the association constants of all drugs except glimepiride. More than 20% increase in the percentage of free drug was observed for gliclazide in the presence of bilirubin and for repaglinide in the presence of bilirubin and hemin. A large decrease was also observed in the percentage of free gliclazide in the presence of hemin, and free glimepiride in the presence of hemin and chloride ions. Competitive binding mechanism has also been proposed. Significant changes (increase/decrease) in the availability of free pharmacologically active antidiabetic drugs, observed in some cases, can result in fluctuations in the blood glucose level of diabetic patients. The effect, which varied with the nature of the drug and the competing substance, was relatively large for gliclazide and repaglinide compared to other drugs.
Related Concept Videos
01:29Drug Distribution: Plasma Protein Binding
01:20Factors Affecting Protein-Drug Binding: Protein-Related Factors
The physicochemical properties of a drug play a significant role in its ability to bind to proteins. Lipophilic drugs, which dissolve in fats, oils, and lipids, can be bound by...
01:22Protein-Drug Binding: Determination Methods
Indirect methods involve isolating the bound drug from its free form in biological samples such as blood, serum, or plasma. These techniques aim to measure the percentage of drugs bound to proteins. Equilibrium dialysis is a commonly used method where the free drug concentration at equilibrium is measured by separating the bound...
01:30Drug Binding to Blood Components
HSA is the most abundant plasma protein and is vital in drug binding. It contains distinct drug-binding sites, with different drugs exhibiting affinity for specific sites. There are three main drug-binding domains for HSA: sites I, II, and III. These domains are further...
01:23Factors Affecting Protein-Drug Binding: Drug Interactions
Displacement interactions can have varying outcomes, ranging from toxicity to virtually...
01:18Factors Affecting Protein-Drug Binding: Drug-Related Factors
One crucial factor in drug-protein binding is the drug's lipophilicity or its affinity for fat. More lipophilic drugs tend to have higher binding extents. For example, highly lipophilic drugs like cloxacillin exhibit substantial protein binding, with as much as 95% of the drug binding to proteins. In contrast,...