title: Molecular binding of toxic phenothiazinium derivatives, azures to bovine serum albumin: A comparative spectroscopic, calorimetric, and in silico study.
abstract: In this paper, the comparative binding behavior of antimalarial drug azure A, azure B and azure C with bovine serum albumin (BSA) has been studied. The interaction has been confirmed by multispectroscopic (UV, fluorescence, Fourier transform infrared (FT-IR), and circular dichroism) and molecular docking techniques. The experimental results show that azure B has the highest BSA binding affinity followed by azure A and azure C. The experimental evidence of binding showed a static quenching mechanism in the interaction azures with BSA. The isothermal titration calorimetry result reveals that the binding was exothermic with positive entropy contribution in each case. The thermodynamic parameters ΔH, ΔG, and ΔS at 25°C were calculated, which indicates that the weak van der Waals forces and hydrogen bonding rather than the hydrophobic effect played an important role in the interaction. According to the theory of Förster nonradiative energy transfer, the distance (r) between the donor (BSA) and acceptor azures found to be <7 nm in all the case. The circular dichroism and FT-IR studies show that the content of α-helix structure has increased for the azures-BSA system. Overall, experimental studies characterize the interaction dynamics and energetics of the binding of three toxic analogs towards the physiologically relevant serum albumins. We hope, the outcome of this work will be most helpful for synthesizing a new type of phenothiazinium derivatives of the better therapeutic application.
authors.affiliation: Department of Chemistry and Chemical Technology, Vidyasagar University, Midnapore, West Bengal, India.
authors.forename: Somnath
authors.initials: S
authors.lastname: Das
authors.affiliation: Department of Chemistry, Aliah University, Kolkata, West Bengal, India.
authors.forename: Md Maidul
authors.initials: MM
authors.lastname: Islam
authors.affiliation: Department of Chemistry and Chemical Technology, Vidyasagar University, Midnapore, West Bengal, India.
authors.forename: Gopal Chandra
authors.initials: GC
authors.lastname: Jana
authors.affiliation: Department of Chemistry and Chemical Technology, Vidyasagar University, Midnapore, West Bengal, India.
authors.forename: Anirudha
authors.initials: A
authors.lastname: Patra
authors.affiliation: SMST, Indian Institute of Technology Kharagpur, Kharagpur, West Bengal, India.
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Jha
authors.affiliation: Department of Chemistry and Chemical Technology, Vidyasagar University, Midnapore, West Bengal, India.
authors.forename: Maidul
authors.identifier: 0000-0003-1408-2273
authors.initials: M
authors.lastname: Hossain
mesh_terms: D000818:Animals; D002151:Calorimetry; D002417:Cattle; D002942:Circular Dichroism; D003198:Computer Simulation; D006860:Hydrogen Bonding; D062105:Molecular Docking Simulation; D010640:Phenothiazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D011485:Protein Binding; D012710:Serum Albumin, Bovine / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013816:Thermodynamics
chemical_list: D010640:Phenothiazines; D012710:Serum Albumin, Bovine; C031637:phenothiazine
keywords: BSA; FTIR; azures; circular dichroism (CD); fluorescence spectroscopy; isothermal titration calorimetry (ITC); molecular docking