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Combination mode of antimalarial drug mefloquine and human serum albumin: Insights from spectroscopic and docking approaches
Author(s) -
Musa Kabiru A.,
Ridzwan Nor F. W.,
Mohamad Saharuddin B.,
Tayyab Saad
Publication year - 2020
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.23337
Subject(s) - human serum albumin , chemistry , circular dichroism , hydrogen bond , docking (animal) , tryptophan , protein secondary structure , stereochemistry , hydrophobic effect , quenching (fluorescence) , fluorescence , fluorescence spectroscopy , crystallography , amino acid , biochemistry , molecule , organic chemistry , medicine , physics , nursing , quantum mechanics
Abstract The interaction between mefloquine (MEF), the antimalarial drug, and human serum albumin (HSA), the main carrier protein in blood circulation, was explored using fluorescence, absorption, and circular dichroism spectroscopic techniques. Quenching of HSA fluorescence with MEF was characterized as static quenching and thus confirmed the complex formation between MEF and HSA. Association constant values for MEF‐HSA interaction were found to fall within the range of 3.79‐5.73 × 10 4 M ˗1 at various temperatures (288, 298, and 308 K), which revealed moderate binding affinity. Hydrogen bonds and hydrophobic interactions were predicted to connect MEF and HSA together in the MEF‐HSA complex, as deduced from the thermodynamic data (Δ S = +133.52 J mol −1 K −1 and Δ H = +13.09 kJ mol −1 ) of the binding reaction and molecular docking analysis. Three‐dimensional fluorescence spectral analysis pointed out alterations in the microenvironment around aromatic amino acid (tryptophan and tyrosine) residues of HSA consequent to the addition of MEF. Circular dichroic spectra of HSA in the wavelength ranges of 200‐250 and 250‐300 nm hinted smaller changes in the protein's secondary and tertiary structures, respectively, induced by MEF binding. Noncovalent conjugation of MEF to HSA bettered protein thermostability. Site marker competitive drug displacement results suggested HSA Sudlow's site I as the MEF binding site, which was also supported by molecular docking analysis.