Effects of Lysozyme on the Activity of Ionic of Fluoroquinolone Species

PEREZ, HUGO; BUSTOS, ANA; TARANTO, MARÍA; FRÍAS, MARÍA; LEDESMA, ANA ESTELA

MOLECULES

MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI

Año: 2018 vol. 23 p. 741 - 760

1420-3049

Fluoroquinolones (FQs) constitute an important class of biologically active broad-spectrumantibacterial drugs that are which are in contact with many biological fluids under different acidityconditions. We studied the reactivity of ciprofloxacin (Cpx) and levofloxacin (Lev) and theirinteraction with lysozyme (Lyz) at different pH values, using UV-visible absorption, fluorescence,infrared spectroscopies supported by DFT calculation and docking. In addition, by antimicrobialassays, the biological consequences of the interaction were evaluated. DFT calculation predictedthat the FQ cationic species present at acid pH have lower stabilization energies, with an electriccharge rearrangement because of their interactions with solvent molecules. NBO and frontier orbitalcalculations evidenced the role of two charged centers, NH2+ and COO−, for interactions by electronicdelocalization effects. Both FQs bind to Lyz via a static quenching with a higher interaction in neutralmedium. The interaction induces a structural rearrangement in β-sheet content while in basic pHa protective effect against the denaturation of Lyz was inferred. The analysis of thermodynamicparameters and docking showed that hydrophobic, electrostatic forces and hydrogen bond are theresponsible of Cpx-Lyz and Lev-Lyz associations. Antimicrobial assays evidenced an antagonisteffect of Lyz in acid medium while in neutral medium the FQs? activities were not modified by Lyz.