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Resumo: A interação entre albumina sérica humana (ASH) e dois derivados biologicamente ativos de 1,4-naftoquinona (FNP e FNP4Br) foi estudada por dicroísmo circular, fluorescência estacionária e fluorescência resolvida no tempo sob condições biológicas a 305 K, 310 K e 315 K. Para oferecer uma explicação a nível molecular, foram realizados cálculos de ancoramento molecular. Uma associação no estado estacionário entre a albumina e as amostras foi observada por estudos espectroscópicos. A ligação é espontânea, moderada, pode perturbar a estrutura secundária da albumina e aumentar a hidrofobicidade ao redor do resíduo Trp-214, isso provavelmente devido a efeitos hidrofóbicos. Parâmetros termodinâmicos e ancoramento molecular sugerem ligação de hidrogênio e interações eletrostáticas (dipolo-dipolo) como as principais forças para a associação ASH:FNP e ASH:FNP4Br.Palavras-chave: Albumina sérica humana; Derivados de 1,4-naftoquinona; Espectroscopia; Ancoramento molecular. AbstractThe interaction between human serum albumin (HSA) and two biologically active 1,4-naphthoquinone derivatives (FNP and FNP4Br) was studied by circular dichroism, steady-state and time-resolved fluorescence under biological conditions at 305 K, 310 K and 315 K. In order to offer a molecular level explanation, molecular docking calculations were carried out. A ground state association between albumin and the samples was observed by spectroscopic studies. The binding is spontaneous, moderate, can perturb the secondary structure of the albumin and increase the hydrophobicity around the Trp-214 residue, probably due the hydrophobic effect. Thermodynamic parameters and molecular docking results suggest hydrogen bonding and electrostatic interactions (dipole-dipole) as the main binding forces for the association HSA:FNP and HSA:FNP4Br.

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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.