The HSA affinity of warfarin and flurbiprofen determined by fluorescence anisotropy measurements of camptothecin |
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| Affiliation: | 1. Departament de Química Física i Analítica, Universitat Jaume I, 12071 Castelló, Spain;2. Departament de Química Analítica, Universitat de València, Av/Doctor Moliner 50, 46100 Burjassot, Valencia, Spain;1. Computational Sciences, Rio de Janeiro State University, Brazil;2. Medical Sciences, Rio de Janeiro State University, Brazil;1. Inorganic Chemistry Department, Faculty of Chemistry, Razi University, Kermanshah, Iran;2. Medical Biology Research Center (MBRC), Kermanshah University of Medical Sciences, Kermanshah, Iran;1. Departamento de Química, Universidade Federal Rural do Rio de Janeiro, BR-465 Km 7, 23970-000 Seropédica, RJ, Brazil;2. Division of Drug Design and Medicinal Chemistry Research Lab, Department of Pharmaceutical Chemistry, Ahalia School of Pharmacy, Palakkad -678557, Kerala, India;3. School of Pure & Applied Physics, M.G. University, Kottayam, India;4. Department of Pharmacology, Grace College of Pharmacy, Palakkad, Kerala, India;5. Department of Pharmaceutical Chemistry, Madras Medical College, Chennai 600004, India |
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| Abstract: | The determination of affinity of warfarin and flurbiprofen to human serum albumin (HSA) by fluorescence anisotropy measurements of carboxylate form of camptothecin (CPT-C) is the subject of this paper. A simple method based on measurements of fluorescence anisotropy of CPT-C allows to determine the affinity constant of CPT-C to HSA by computation of the fraction of bound CPT-C molecules with HSA It was observed, that adding of competing drug to plasma significant reduces the rate of increase of CPT-C fluorescence anisotropy with increase of albumin concentration and, the affinity constant of CPT-C to HSA decreases. The hypothesis of interactions between competing drug and CPT-C is presented. The results of these studies suggest that CPT-C displaces other drug from protein binding site and the degree of this displacement depends on concentration of drug and drug-HSA binding affinity. The presented in this paper biosystems research allows to estimate the affinity constant of warfarin and flurbiprofen. It was also confirmed that despite that most of drugs bind predominantly to Site I or Site II of HSA (only one of these sites is high-affinity site), at elevated concentrations, part of drug molecules can be bound to low-affinity site of HSA. |
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