Horizontal comparison of "red or blue shift" and binding energy of six fluoroquinolones: Fluorescence quenching mechanism, theoretical calculation and molecular modeling method

Abstract

In this article, the interaction between six fluoroquinolones (FQs) and bovine serum albumin (BSA) was initially studied at 298 K, 303 K and 310 K respectively under simulated physiological conditions by fluorescence spectroscopy. At the same time, the sub-structural domains on BSA that may bind to FQs were investigated by molecular docking simulation technique. A combination of quantitative and qualitative approaches was used in the analysis of the binding constants, binding sites and corresponding thermodynamic parameters in the interaction system, it was found that FQs forms a complex with BSA and undergoes static quenching, which is the main cause of fluorescence quenching. The results indicated that hydrogen bonds, Van der Waals force and electrostatic interaction were the main binding forces between the complexes, it also showed that these six fluoroquinolones mainly bound to the IIA and IIIA structural domains of BSA, while DANO and SARA may be more toxic than other antibiotics. Based on Foster's non-radiative energy transfer theory, the binding distance between FQs and BSA was calculated to be less than 7 nm, indicating the existence of energy transfer between small molecule drugs and proteins. Synchronous fluorescence and UV-Vis absorption spectroscopy further confirmed that FQs can alter the secondary conformational change of BSA. Lomefloxacin has a different effect from the other five fluoroquinolone antibiotics because it causes a decrease in polarity and an increase in hydrophobicity around tryptophan residues, while the other five FQs have the opposite effect. Together, the study of FQs-BSA is of great significance to elucidate the pharmacokinetics and pharmacodynamics of FQs.

Keywords: BSA; Fluoroquinolones; Molecular docking; Multi-spectroscopy methods; Quenching.