Mechanism of interaction of hypoglycemic agents glimepiride and glipizide with human serum albumin

AbstractThe mechanism of interaction of hypoglycemic drugs, glimepiride and glipizide with human serum albumin (HSA) has been studied using fluorescence spectroscopy. The results are discussed in terms of the binding parameters, thermodynamics of the binding process, nature of forces involved in the interaction, identification of drug binding site on serum albumin and the fluorescence quenching mechanism involved. The association constants were of the order of 105 and glipizide was found to have much higher affinity for HSA than glimepiride at all temperatures. Thermodynamic parameters for the binding suggested that hydrophobic interactions are primarily involved in the binding of these drugs to HSA. However, glimepiride and glipizide appear to cause temperature-dependent conformational changes in the albumin molecule and, therefore, the nature of interaction varied with temperature. Glimepiride and glipizide bind to both site I and site II on HSA, but the primary interaction occurs at site II. The binding region in site II is different for the two drugs. Stern-Volmer analysis of quenching data indicated that tryptophan residues of HSA are not fully accessible to the drugs and a predominantly dynamic quenching mechanism is involved in the binding. Results can provide useful insight into prediction of competitive displacement of these drugs by other co-administered drugs and excipients, resulting in serious fluctuations of the blood glucose levels in diabetic patients.

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BINDING STUDIES OF VALGANCICLOVIR TO HUMAN SERUM ALBUMIN BY MULTISPECTROSCOPIC TECHNIQUES

International Journal of Pharmacy and Pharmaceutical Sciences ◽

10.22159/ijpps.2018v10i10.28090 ◽

2018 ◽

Vol 10 (10) ◽

pp. 87

Author(s):

Lade Somaji ◽

Ravi Rapolu

Keyword(s):

Molecular Modeling ◽

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Conformational Changes ◽

Binding Constant ◽

Electrostatic Interactions ◽

Hydrophobic Interactions ◽

Experimental Studies ◽

Binding Studies

Objective: The aim of the present study was to investigate the mode and mechanism of interactions involved towards binding of valganciclovir (VGC) with Human Serum Albumin (HSA) by spectroscopic and molecular modeling studies which can be extrapolated for the ten folds increase of bioavailability over its prodrug galanciclovir.Methods: Herein we employed fluorescence spectroscopy for evaluating the binding constant value, site of interaction and changes in the microenvironment of HSA fluorophores. Circular dichroism (CD) and UV-Visible spectroscopy is used for conformational changes of HSA in the event of binding of valaganciclovir. These experimental studies were further corroborated with molecular modeling studies.Results: Considerable quenching of fluorescence intensities of fluorophores in the presence of VGC showed that VGC interacts with HSA strongly with a binding constant of 4.11x104 M-1 with a free energy change of-6.26 Kcal/mol. Synchronous fluorescence and CD studies show that the microenvironment and confirmation of HSA are slightly altered in the presence of VGC. Though site marker experiments does not give any clue for identification of site, molecular docking studies showed that VGC binds to site IB of HSA.Conclusion: The weaker dominant electrostatic interactions with minor contributions of hydrophobic interactions of VGC with HSA at site IB (catalytic domain) might be the probable reason for the relative increase of hydrolysis of VGC to galanciclovir. And moderate binding constant value with HSA implies that HSA can be able to transport VGC under physiological conditions.

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The Influence of Oxidative Stress on Serum Albumin Structure as a Carrier of Selected Diazaphenothiazine with Potential Anticancer Activity

Pharmaceuticals ◽

10.3390/ph14030285 ◽

2021 ◽

Vol 14 (3) ◽

pp. 285

Author(s):

Małgorzata Maciążek-Jurczyk ◽

Beata Morak-Młodawska ◽

Małgorzata Jeleń ◽

Wiktoria Kopeć ◽

Agnieszka Szkudlarek ◽

...

Keyword(s):

Human Serum Albumin ◽

Serum Albumin ◽

Human Serum ◽

Anticancer Activity ◽

Drug Distribution ◽

Cd Spectroscopy ◽

Drug Binding ◽

Protein Activity ◽

Chloramine T ◽

The Stability

Albumin is one of the most important proteins in human blood. Among its multiple functions, drug binding is crucial in terms of drug distribution in human body. This protein undergoes many modifications that are certain to influence protein activity and affect its structure. One such reaction is albumin oxidation. Chloramine T is a strong oxidant. Solutions of human serum albumin, both non-modified and modified by chloramine T, were examined with the use of fluorescence, absorption and circular dichroism (CD) spectroscopy. 10H-3,6-diazaphenothiazine (DAPT) has anticancer activity and it has been studied for the first time in terms of binding with human serum albumin—its potential as a transporting protein. Using fluorescence spectroscopy, in the presence of dansylated amino acids, dansyl-l-glutamine (dGlu), dansyl-l-proline (dPro), DAPT binding with two main albumin sites—in subdomain IIA and IIIA—has been evaluated. Based on the conducted data, in order to measure the stability of DAPT complexes with human (HSA) and oxidized (oHSA) serum albumin, association constant (Ka) for ligand-HSA and ligand-oHSA complexes were calculated. It has been presumed that oxidation is not an important issue in terms of 10H-3,6-diazaphenothiazine binding to albumin. It means that the distribution of this substance is similar regardless of changes in albumin structure caused by oxidation, natural occurring in the organism.

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