title: Exploring the interaction between the antiallergic drug, tranilast and human serum albumin: Insights from calorimetric, spectroscopic and modeling studies.
abstract: The interaction of tranilast (TRN), an antiallergic drug with the main drug transporter in human circulation, human serum albumin (HSA) was studied using isothermal titration calorimetry (ITC), fluorescence spectroscopy and in silico docking methods. ITC data revealed the binding constant and stoichiometry of binding as (3.21 ± 0.23) × 10(6)M(-1) and 0.80 ± 0.08, respectively, at 25°C. The values of the standard enthalpy change (ΔH°) and the standard entropy change (ΔS°) for the interaction were found as -25.2 ± 5.1 kJ mol(-1) and 46.9 ± 5.4 J mol(-1)K(-1), respectively. Both thermodynamic data and modeling results suggested the involvement of hydrogen bonding, hydrophobic and van der Waals forces in the complex formation. Three-dimensional fluorescence data of TRN-HSA complex demonstrated significant changes in the microenvironment around the protein fluorophores upon drug binding. Competitive drug displacement results as well as modeling data concluded the preferred binding site of TRN as Sudlow's site I on HSA.
authors.affiliation: Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia; Centre of Research for Computational Sciences and Informatics for Biology, Bioindustry, Environment, Agriculture and Healthcare (CRYSTAL), Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. Electronic address: saadtayyab2004@yahoo.com.
authors.forename: Saad
authors.initials: S
authors.lastname: Tayyab
authors.affiliation: Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Mohammed S
authors.initials: MS
authors.lastname: Zaroog
authors.affiliation: Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Shevin R
authors.initials: SR
authors.lastname: Feroz
authors.affiliation: Centre of Research for Computational Sciences and Informatics for Biology, Bioindustry, Environment, Agriculture and Healthcare (CRYSTAL), Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia; Bioinformatics Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Saharuddin B
authors.initials: SB
authors.lastname: Mohamad
authors.affiliation: Biomolecular Research Group, Biochemistry Programme, Institute of Biological Sciences, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia.
authors.forename: Sri Nurestri A
authors.initials: SN
authors.lastname: Malek
mesh_terms: D018926:Anti-Allergic Agents / Q000737:chemistry*; D001665:Binding Sites; D001667:Binding, Competitive; D002151:Calorimetry; D019277:Entropy; D006801:Humans; D008956:Models, Chemical; D008958:Models, Molecular; D062105:Molecular Docking Simulation; D012709:Serum Albumin / Q000737:chemistry; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013816:Thermodynamics; D062367:ortho-Aminobenzoates / Q000737:chemistry*
chemical_list: D018926:Anti-Allergic Agents; D012709:Serum Albumin; D062367:ortho-Aminobenzoates; C012293:tranilast
keywords: Human serum albumin; Isothermal titration calorimetry; Ligand binding; Molecular docking; Tranilast