Fluoroquinolones as Tyrosinase Inhibitors; Enzyme Kinetics and Molecular Docking Studies to Explore Their Mechanism of Action

Abstract

The binding of fluoroquinolones, the most commonly prescribed antibiotics, with melanin is well explored. However, their binding patterns and exact mechanism of interaction with tyrosinase, a key enzyme in melanogenesis, are not explored yet. Thus, in the present study, seven fluoroquinolone drugs were selected to characterize their interactions with the tyrosinase enzyme: ciprofloxacin, enoxacin sesquihydrate, ofloxacin, levofloxacin, sparfloxacin, moxifloxacin and gemifloxacin. The results confirmed that all the drugs execute excellent enzyme activity, with an inhibition range from IC50 = 28 ± 4 to 50 ± 1.9 μM, outperforming the standard hydroquinone (IC50 = 170 μM). Later, kinetic studies revealed that all the drugs showed irreversible, but mixed-type, tyrosinase inhibition, with a preferentially competitive mode of action. Further, 2D and 3D docked complexes and binding analyses confirmed their significant interactions in the active region of the target enzyme, sufficient for the downstream signaling responsible for the observed tyrosinase inhibition. Thus, this is the first report demonstrating their mechanism of tyrosinase inhibition, critical for melanin-dependent responses, including toxicity.

Keywords

• fluoroquinolone
• antibiotic
• tyrosinase
• enzyme kinetic
• molecular docking