Multiple Spectroscopic and Theoretical Approaches to Study the Interaction between HSA and the Antiparasitic Drugs: Benznidazole, Metronidazole, Nifurtimox and Megazol

Abstract

The interaction between four antiparasitic drugs (benznidazole (BZL), metronidazole (MTZ), nifurtimox (NFX) and megazol (MZ)) with human serum albumin (HSA), the main vehicle of biodistribution of xenobiotics, hydrophobic, small and endogenous molecules in the bloodstream, was evaluated by multiple spectroscopic techniques and theoretical calculations. In all cases quenching of the fluorescence of HSA by these drugs involve a static mechanism, due to ground state association. There is just one main binding site in HSA for these four ligands (Sudlow's site I); binding is spontaneous, moderate, does not have any effect on the polarity around the Tyr and Trp residues and does not perturb significantly the secondary structure of the protein. Molecular docking studies suggest hydrogen bonding and hydrophobic interactions as the main binding forces, i.e., BZL associates with the Trp-214 residue via hydrophobic interactions and with Gln-220, Arg-221 and Glu-449 residues via hydrogen bonding; whereas MTZ associates with Leu-197 and Leu-480 residues via hydrophobic interactions and with Trp-214, Glu-449 and Ser-453 via hydrogen bonding. Furthermore, electrostatic interactions were also suggested for HSA:MZ and HSA:NFX.

Acridine Based N-Acylhydrazone Derivatives as Potential Anticancer Agents: Synthesis, Characterization and ctDNA/HSA Spectroscopic Binding Properties

“…Synchronous emission spectroscopy is fluorescence spectroscopy performed at a constant wavelength, and the technique to provide information on the effect of the binding of small molecules on the microenvironment in the vicinity of tryptophan (Trp) and tyrosine (Tyr) as chromophore residues of protein [51]. Synchronous fluorescence spectra assay simultaneously records the excitation and emission monochromators at a constant wavelength interval; the characteristic spectra of Tyr and Trp residues are found at ∆λ = 15 or 60 nm [48,51]. The shift in the position of fluorescence emission maximum corresponds to changes in the polarity around the chromophore molecule [52].…”

“…The shift in the position of fluorescence emission maximum corresponds to changes in the polarity around the chromophore molecule [52]. Specifically, a red shift indicates the increment of hydrophilicity, and a blue shift reveals the increment of hydrophobicity around the fluorophores of serum albumins [48,51]. As is shown in Figures 3 and S4, the fluorescence intensity of the synchronous emission spectra of HSA was found to decrease with increasing amounts of acridine derivatives 3a-3d, a result which further demonstrates the occurrence of fluorescence quenching in the binding process.…”

“…The evidently higher rate reduces the fluorescence intensity around Trp, further indicating that the binding site is site I in the IIA HSA subdomain. A useful method for studying drug-HSA interactions is three-dimensional fluorescence spectroscopy, which can offer information about the structural changes to the polypeptide backbone structure and the microenvironment polarity around the Trp and Tyr residues [49][50][51][53][54][55][56][57][58][59]. The results of 3D fluorescence are shown in Figures 4 and S6.…”

Quenching of Protein Fluorescence by Fullerenol C60(OH)36 Nanoparticles

“…Two important binding sites on human serum albumin are Sudlow site I and site II, which are located in subdomains IIA and IIIA, respectively [ 24 , 25 , 27 ]. The protein is formed by 585 amino acid residues containing 17 disulfide bridges and a single tryptophan residue (Trp-214) located in the hydrophobic cavity of site I [ 26 , 28 ]. The binding affinity offered by site I is mainly executed through hydrophobic interactions, whilst the affinity of site II involves a combination of hydrophobic, hydrogen bonding, and electrostatic interactions [ 29 ].…”

Study on the interaction of two quinazoline derivatives as novel PI3K/mTOR dual inhibitors and anticancer agents to human serum albumin utilizing spectroscopy and docking

“…[6] As the most abundant protein in the plasma of human beings, HSA is $60% of the total protein in plasma and helps to maintain $80% of the human body's osmotic pressure. [7][8][9] It is widely known that HSA can bind to a series of endogenous and exogenous ligands with an association constant that ranges from moderate to high (10 4 -10 6 L/mol) [10] and plays a critical function in the transit and disposal of these ligands in the blood, such as aliphatic acids, nutrient substances, some metallic ions, hormones, enzymes, metabolites, as well as many therapeutic drugs. [11,12] When a medication enters the human body, a reversible binding occurs to form medication-protein complexes, which can be stored or carried to various target cells or tissues.…”