Probing the potential toxicity of trimetazidine by characterizing its interaction with human serum albumin

The small molecular drugs pharmacodynamics and pharmacokinetics could be affected by human serum albumin (HSA) transport, so we studied the interaction between HSA and the widely used anti-ischemic agent, trimetazidine (TMZ), using different approaches. As shown by synchronous fluorescence spectroscopy, the interaction affects the microenvironment confirmation around tyrosine residues. The site-competitive experiments showed that TMZ had an affinity toward subdomain III A (site II) of HSA. The enthalpy and entropy changes (ΔH and ΔS), which were 37.75 and 0.197 K J mol−1, respectively, showed that the predominant intermolecular interactions are hydrophobic forces. According to FTIR research, the interaction between HSA and TMZ caused polypeptide carbonyl-hydrogen bonds to rearrange. The HSA esterase enzyme activity was decreased with TMZ. Docking analysis confirmed the site-competitive experiments and thermodynamic results. This study demonstrated that TMZ interacted with HSA, and the structure and function of HSA were influenced by TMZ. This study could aid in understanding the pharmacokinetics of TMZ and provide basic data for safe use.

[1]  P. Verma,et al.  Spectroscopic studies of binding interactions of 2-chloroethylphenyl sulphide with bovine serum albumin , 2021 .

[2]  A. Nikiforova,et al.  Binding Constants of Clinical Drugs and Other Organic Ligands with Human and Mammalian Serum Albumins , 2021, Biophysica.

[3]  M. Mabrouk,et al.  One-Pot Synthesis of Fluorescent Nitrogen and Sulfur-Carbon Quantum Dots as a Sensitive Nanosensor for Trimetazidine Determination. , 2021, Luminescence : the journal of biological and chemical luminescence.

[4]  Neelam,et al.  Layer by layer controlled synthesis at room temperature of tri‐modal ( MRI , fluorescence and CT ) core/shell superparamagnetic IO /human serum albumin nanoparticles for diagnostic applications , 2021 .

[5]  M. Mabrouk,et al.  A Novel Eplerenone Ecofriendly Fluorescent Nanosensor Based on Nitrogen and Sulfur-Carbon Quantum Dots , 2020, Journal of Fluorescence.

[6]  H. Ahmed,et al.  The use of complex formation approach for spectroscopic analysis of certain oral hypoglycemic with Eosin Y , 2019, Microchemical Journal.

[7]  M. Alajmi,et al.  Insight of the Interaction between 2,4-thiazolidinedione and Human Serum Albumin: A Spectroscopic, Thermodynamic and Molecular Docking Study , 2019, International journal of molecular sciences.

[8]  H. Ahmed,et al.  The use of SDS micelles as additive to increase fluorescence analysis of sitagliptin and saxagliptin derivatives in their tablets and human plasma , 2019, Microchemical Journal.

[9]  Rajan Patel,et al.  Esterase activity and conformational changes of bovine serum albumin toward interaction with mephedrone: Spectroscopic and computational studies , 2018, Journal of molecular recognition : JMR.

[10]  K. Ahmad,et al.  Binding of Tolperisone Hydrochloride with Human Serum Albumin: Effects on the Conformation, Thermodynamics, and Activity of HSA. , 2018, Molecular pharmaceutics.

[11]  A. Kadi,et al.  Biophysical and In Silico Studies of the Interaction between the Anti-Viral Agents Acyclovir and Penciclovir, and Human Serum Albumin , 2017, Molecules.

[12]  Won-Kyung Cho,et al.  Biophysical Study on the Interaction between Eperisone Hydrochloride and Human Serum Albumin Using Spectroscopic, Calorimetric, and Molecular Docking Analyses. , 2017, Molecular pharmaceutics.

[13]  A. Alanazi,et al.  Fluorescence spectroscopic and molecular docking studies of the binding interaction between the new anaplastic lymphoma kinase inhibitor crizotinib and bovine serum albumin. , 2017, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[14]  P. Alam,et al.  Insight into the interaction of antitubercular and anticancer compound clofazimine with human serum albumin: spectroscopy and molecular modelling , 2017, Journal of biomolecular structure & dynamics.

[15]  J. Camm,et al.  Medical treatment of stable angina: A tailored therapeutic approach. , 2016, International journal of cardiology.

[16]  C. Dézsi.  Trimetazidine in Practice: Review of the Clinical and Experimental Evidence , 2016, American journal of therapeutics.

[17]  A. Amorim,et al.  Fluorescence and Docking Studies of the Interaction between Human Serum Albumin and Pheophytin , 2015, Molecules.

[18]  Anil H. Gore,et al.  Spectroscopic analysis on the binding interaction of biologically active pyrimidine derivative with bovine serum albumin☆ , 2015, Journal of pharmaceutical analysis.

[19]  R. H. Khan,et al.  Biophysical investigation of thymoquinone binding to ‘N’ and ‘B’ isoforms of human serum albumin: exploring the interaction mechanism and radical scavenging activity , 2015 .

[20]  Narayani Ghosh,et al.  Hydrophobicity is the governing factor in the interaction of human serum albumin with bile salts. , 2015, Langmuir : the ACS journal of surfaces and colloids.

[21]  R. H. Khan,et al.  Effect of copper oxide nanoparticles on the conformation and activity of β-galactosidase. , 2014, Colloids and surfaces. B, Biointerfaces.

[22]  R. Subramanyam,et al.  Binding studies of L-3,4-dihydroxyphenylalanine with human serum albumin. , 2014, Molecular bioSystems.

[23]  Y. Shokoohinia,et al.  Studies of the Interaction between Isoimperatorin and Human Serum Albumin by Multispectroscopic Method: Identification of Possible Binding Site of the Compound Using Esterase Activity of the Protein , 2013, TheScientificWorldJournal.

[24]  S. Jain,et al.  BIOTECHNOLOGICALLY RELEVANT ENZYMES AND PROTEINS Structural characteristics of thermostable immunogenic outer membrane protein from Salmonella enterica serovar Typhi , 2014 .

[25]  N. Subbarao,et al.  Biophysical insight into furosemide binding to human serum albumin: a study to unveil its impaired albumin binding in uremia. , 2013, The journal of physical chemistry. B.

[26]  Uttam Pal,et al.  Nickel(II)-Schiff base complex recognizing domain II of bovine and human serum albumin: spectroscopic and docking studies. , 2012, Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy.

[27]  Ejaz Ahmad,et al.  pH-Induced Molten Globule State of Rhizopus niveus Lipase is More Resistant Against Thermal and Chemical Denaturation Than Its Native State , 2012, Cell Biochemistry and Biophysics.

[28]  Guowen Zhang,et al.  Fluorescence spectrometric studies on the binding of puerarin to human serum albumin using warfarin, ibuprofen and digitoxin as site markers with the aid of chemometrics , 2011 .

[29]  J. Chamani,et al.  Probing the Interaction of Human Serum Albumin with Norfloxacin in the Presence of High-Frequency Electromagnetic Fields: Fluorescence Spectroscopy and Circular Dichroism Investigations , 2011, Molecules.

[30]  R. Bhat,et al.  Stereo-Selectivity of Human Serum Albumin to Enantiomeric and Isoelectronic Pollutants Dissected by Spectroscopy, Calorimetry and Bioinformatics , 2011, PloS one.

[31]  Lorenzo Stella,et al.  Fluorescence quenching and ligand binding: A critical discussion of a popular methodology , 2011 .

[32]  Edward H. Kerns,et al.  The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery , 2010, Nature Reviews Drug Discovery.

[33]  S. S. Kalanur,et al.  Interaction of Bioactive Coomassie Brilliant Blue G with Protein: Insights from Spectroscopic Methods , 2010, Scientia pharmaceutica.

[34]  S. Curry,et al.  Crystallographic Analysis of Human Serum Albumin Complexed with 4Z,15E-Bilirubin-IXα , 2008, Journal of molecular biology.

[35]  S. Ozkan,et al.  Trimetazidine revisited: a comprehensive review of the pharmacological effects and analytical techniques for the determination of trimetazidine. , 2008, Cardiovascular therapeutics.

[36]  A. Sułkowska,et al.  Interaction of drugs with bovine and human serum albumin , 2002 .

[37]  S. Curry,et al.  Binding of the General Anesthetics Propofol and Halothane to Human Serum Albumin , 2000, The Journal of Biological Chemistry.

[38]  G. Park,et al.  The role of albumin in critical illness. , 2000, British journal of anaesthesia.

[39]  S. Tanase,et al.  Role of arg-410 and tyr-411 in human serum albumin for ligand binding and esterase-like activity. , 2000, The Biochemical journal.

[40]  Thomas Lengauer,et al.  Computational methods for biomolecular docking. , 1996, Current opinion in structural biology.

[41]  J. Doweiko,et al.  Reviews: Role of Albumin in Human Physiology and Pathophysiology , 1991 .

[42]  P. Ross,et al.  Thermodynamics of protein association reactions: forces contributing to stability. , 1981, Biochemistry.

[43]  D. Wade,et al.  Spectroscopic techniques in the study of protein binding. A fluorescence technique for the evaluation of the albumin binding and displacement of warfarin and warfarin‐alcohol , 1975, Clinical and experimental pharmacology & physiology.

[44]  M. Rashidi,et al.  Interaction of norfloxacin with bovine serum albumin studied by different spectrometric methods; displacement studies, molecular modeling and chemometrics approaches , 2015 .

[45]  BMC Structural Biology BioMed Central , 2007 .