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.

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.…”