Study the interactions between human serum albumin and two antifungal drugs: Fluconazole and its analogue DTP |
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| Institution: | 1. Faculty of Health Sciences, University of Macau, Macau, China;2. School of Pharmacy, Xuzhou Medical College, Xuzhou, Jiangsu 221004, China;1. School of Medicine, University of Belgrade, University Clinic for Gynecology and Obstetrics “Narodni front”, Belgrade, Serbia;2. School of Medicine, University of Belgrade, Clinic for Gastroenterology and Hepatology, Clinical Centre of Serbia, Belgrade, Serbia;1. Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt;2. Pharmacognosy Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef, Egypt;3. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta T6G 2N8, Canada;1. Division of Nephrology, University of Pennsylvania, Philadelphia, PA;2. Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA;3. Abramson Cancer Center of the University of Pennsylvania, Philadelphia, PA;4. The Children''s Hospital of Philadelphia, Philadelphia, PA;1. Chemistry Division, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India;2. Biophysical Chemistry Laboratory, CSIR-Indian Institute of Chemical Biology, Kolkata 700 032, India;1. Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602, United States;2. Rega Institute for Medical Research, KU Leuven, B-3000 Leuven, Belgium;1. Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA;2. Department of Pharmacology, University of Arizona, Tucson, AZ 85721, USA |
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| Abstract: | Binding affinities of fluconazole and its analogue 2-(2,4-dichlorophenyl)-1,3-di(1H-1,2,4-triazol-yl)-2-propanol (DTP) to human serum albumin (HSA) were investigated under approximately human physiological conditions. The obtained result indicated that HSA could generate fluorescent quenching by fluconazole and DTP because of the formation of non-fluorescent ground-state complexes. Binding parameters calculated from the Stern–Volmer and the Scatchard equations showed that fluconazole and DTP bind to HSA with binding affinities of the order 104 L/mol. The thermodynamic parameters revealed that the binding was characterized by negative enthalpy and positive entropy changes, suggesting that the binding reaction was exothermic. Hydrogen bonds and hydrophobic interaction were found to be the predominant intermolecular forces stabilizing the drug–protein. The effect of metal ions on the binding constants of fluconazole–HSA complex suggested that the presence of Mg2+ and Zn2+ ions could decrease the free drug level and extend the half-life in the systematic circulation. Docking experiments revealed that fluconazole and DTP binds in HSA mainly by hydrophobic interaction with the possibility of hydrogen bonds formation between the drugs and the residues Arg 222, Lys 199 and Lys 195 in HSA. |
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| Keywords: | Fluconazole Human serum albumin Binding affinity Fluorescence spectrum Molecular docking |
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