A pair of homoisoflavonoid analogues (6-aldehydo-isoophiopogonanone A/6-aldehydo-isoophiopogonanone B) from Ophiopogon japonicus as a tyrosinase inhibitor: inhibitory activity, conformational change and mechanism

In this research, the inhibition mechanism of a pairs of homoisoflavonoid analogues (6-aldehydo-isoophiopogonanone A (AIO-A) and 6-aldehydo-isoophiopogonanone B (AIO-B)) on tyrosinase (Tyr) was investigated by multi-spectroscopic techniques combined with molecular docking. The results demonstrated that AIO-A suppressed the activity of Tyr in a reversible competitive-inhibition with a half inhibitory concentration (IC50) of (12.67 ± 2.52) × 10 –5 molˑL −1 , while AIO-B was a reversible mixed-inhibition with IC50 of (4.81 ± 0.74) × 10 –5 molˑL −1 . AIO-A/AIO-B bound to Tyr driven by the intermolecular interactions, including van der Waals interaction, hydrogen bonding and hydrophobic interaction, thereby resulted in a secondary structure change of Tyr and its intrinsic fluorescence quenching. The molecular docking revealed that an aldehyde oxygen atom in AIO-A and methoxyphenyl in AIO-B formed coordination with two Cu ions in the active center of Tyr protein. It can be deduced that the coordination with two Cu ions may prevent the entrance of substrate and then inhibit the catalytic activity of Tyr. The research might provide new perspectives on the inhibition mechanism of AIO-A and AIO-B on Tyr and functional research for the prevention and treatment of pigmented skin diseases and anti-browning of homoisoflavonoids as a food supplement.