Molecules 2017, 22(12), 2249; doi:10.3390/molecules22122249
In Vitro Investigation of the Interaction of Tolbutamide and Losartan with Human Serum Albumin in Hyperglycemia States
School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Chair and Department of Physical Pharmacy, Jagiellońska 4, Medical University of Silesia, 41-200 Sosnowiec, Poland
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Received: 20 November 2017 / Revised: 9 December 2017 / Accepted: 15 December 2017 / Published: 17 December 2017
(This article belongs to the Section Medicinal Chemistry)
Abstract
Serum albumin is exposed to numerous structural modifications which affect its stability and activity. Glycation is one of the processes leading to the loss of the original properties of the albumin and physiological function disorder. In terms of long lasting states of the hyperglycemia, Advanced Glycation End-products (AGEs) are formed. AGEs are responsible for cellular and tissue structure damage that cause the appearance of a number of health consequences and premature aging. The aim of the present study was to analyze the conformational changes of serum albumin by glycation—“fructation”—using multiple spectroscopic techniques, such as absorption (UV-Vis), fluorescence (SFM), circular dichroism (CD) and nuclear magnetic resonance (NMR) spectroscopy and evaluate of possible alteration of binding and competition between tolbutamide (TB, a first-generation sulfonylurea oral hypoglycemic drug) and losartan (LOS, an angiotensin II receptor (AT1) blocker used in hypertension (1st line with a coexisting diabetes)) in binding to non-glycated (HSA) and glycated (gHSAFRC) human serum albumin in high-affinity binding sites. The studies allowed us to indicate the structural alterations of human serum albumin as a result of fructose glycation. Changes in binding parameters, such as associationKeywords:
glycation; drug-drug-albumin binding; SFM; UV-Vis; CD and 1H-NMR spectroscopy
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Szkudlarek, A.; Pentak, D.; Ploch, A.; Pożycka, J.; Maciążek-Jurczyk, M. In Vitro Investigation of the Interaction of Tolbutamide and Losartan with Human Serum Albumin in Hyperglycemia States. Molecules 2017, 22, 2249.
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