Reversible Binding of Antidiabetic Drugs, Repaglinide and Gliclazide, with Human Serum Albumin

Abstract

Mechanism of interaction of antidiabetic drugs, repaglinide and gliclazide, to human serum albumin has been studied using fluorescence spectroscopic technique. Repaglinide had much higher affinity for human serum albumin when compared with gliclazide. The order of association constants was 10(5) for both the drugs. The size, hydrophobicity and flexibility of the drug molecules play a major role in explaining the binding behaviour of these drugs. Hydrophobic interactions are predominantly involved in the binding. However, drugs do not share common sites with 1-anilinonaphthalene-8-sulphonate on the human serum albumin molecule. Both tyrosine and tryptophan residues participate in the interaction. Repaglinide and gliclazide are bound to site II on the human serum albumin molecule, and the aromatic ring of 411Tyr appears to be involved in binding within site II. Although they do not bind at site I, their binding at site II may cause conformational changes thereby affecting the binding of other ligands to site I. Site-specificity can be useful in predicting the competitive displacement of these drugs by other co-administered drugs, resulting in fluctuations of the blood glucose levels in diabetic patients. Stern-Volmer analysis of quenching data indicated that the tryptophan residues are not fully accessible to the drugs and predominantly dynamic quenching mechanism is involved in the binding.

Stereoselective binding of chiral anti-diabetic drug nateglinide to plasma proteins

“…The difference in the binding affi nity between results reported by other authors and presented here could be due to different techniques used. It is well known that the racemate and enantiomers of meglitinide type antidiabetics are strongly bound to HSA stereoselectively (16) .…”

Fluorescence spectroscopic study for competitive binding of antidiabetic drugs and endogenous substances on serum albumin

“…The linearity of both the plots showed that the tryptophan residues of HSA are fully accessible to bilirubin and hemin. The quenching constants ( K q ), calculated from the simple Stern-Volmer equation is predominantly involved because dynamic quenching usually leads to a downward curvature in the plots [ 13 ]. Because K q = k q τ 0 , the corresponding rate constant for quenching ( k q ), calculated from K q values, were of the order of 10 13 and 10 14 for bilirubin and hemin, respectively.…”

Studies on the binding of a carditionic agent to human serum albumin by two-dimensional correlation fluorescence spectroscopy and molecular modeling

“…Because of this, many pharmaceutical firms have developed and standardized screens for HSA binding in the first step of new drug design. Therefore, the studies on the binding of a bioactive compound to HSA have been an important research field in chemistry, life sciences and clinical medicine [4][5][6][7][8][9][10].…”