Combination mode of antimalarial drug mefloquine and human serum albumin: Insights from spectroscopic and docking approaches

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 × 104 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 (ΔS = +133.52 J mol−1 K−1 and ΔH = +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.

Effects of black cumin-based antimalarial drug loaded with nano-emulsion of bovine and human serum albumins by spectroscopic and molecular docking studies

“…There was a red shift from 334 to 337 nm in HSA and 320–324 nm BSA after adding MEF loaded Black cumin nanoemulsion oil nanoemulsion. When MEF was added to the HSA solution, the FI at 343 nm gradually decreased and at the highest MEF concentration (27 M), a 49% percent reduction in the FI was observed [ 9 ]. 27 M concentration of Mefloquine in the sample with BSA and HSA, In the figure it was mentioned the total concentration of drug-loaded formulation with protein compounds In addition, at 27 M MEF concentration, there was a slight (2 nm) blue shift in HSA emission maxima.…”

“…In general, quenching mechanisms can be divided into two types: dynamic and static [ 16 ]. In contrast to static quenching, dynamic quenching achieved through collision and energy transfer does not produce any change in the UV spectrum of biomolecules upon engagement with the quencher [ 9 ].The UV–Visible absorbance and fluorescence emission of both nanoemulsion systems varied, indicating that the mechanism is static in nature. Regardless of the mechanism, fluorescence emission spectra were effective in obtaining information about changes in the protein's aromatic microenvironment [ 12 ].…”

“…Using the experimental parameters listed in the instruction manual, the three-dimensional fluorescence spectra of HSA and BSA were measured [ 9 , 28 ]. The start and end wavelengths of excitation and emission were adjusted at 300 and 500 nm, respectively [ 18 ].…”

“…In summary, nanocarrier interactions with proteins cause structural conformational changes by exposing novel epitopes on the protein's surface [ 8 ]. As a result, research into the interaction of essential oil-based nanoemulsions with biological proteins has emerged as a major topic in biomedical research, with the goal of learning more about the structural changes that can occur [ [9] , [10] , [11] ]. In blood plasma, serum albumin is still the most abundant carrier protein.…”

Roles of Virtual Screening and Molecular Dynamics Simulations in Discovering and Understanding Antimalarial Drugs

“…In the study of Musa and coworkers [101], the docking calculations supported that Mefloquine prefers to bind to Site I based on a more negative lowest binding energy upon binding to Site I (approximately −27 kJ mol −1 ) than to Site II (approximately −23 kJ mol −1 ). Amino acids Tyr150 and Arg257 were seen to form hydrogen bonds with mefloquine [101]. Another drug, Lumefantrine (Figure 14), is used in combination with other antimalarial drugs to treat malaria.…”