Potent Antioxidant and Anti-Tyrosinase Activity of Butein and Homobutein Probed by Molecular Kinetic and Mechanistic Studies †
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Inhibited Autoxidation Studies in Micelles
2.3. Electron Paramagnetic Resonance (EPR) Spectroscopy
2.4. Tyrosnase Inbibition
2.5. Stability of Inhibitors in the Presence of Oxygen
2.6. Molecular Docking
2.7. Statistical Analysis
3. Results and Discussion
3.1. Antioxidant Activity in the Inhibited Autoxidation of Methyl Linoleate Micelles
3.2. EPR Spectroscopy
3.3. Explaining the Excellent Antioxidant Activity of Butein in MeLin Micelles
3.4. Kinetics of Inhibition of Mushroom Tyrosinase (mTYR)
3.5. Determination of IC50 against mTYR
3.6. Molecular Docking
3.7. Stability of Butein and Homobutein toward Air and mTYR
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Antioxidant | kinh/103 M−1s−1 | n | BDEOH/kcal/mol |
---|---|---|---|
Butein | 29.8 ± 9.2 | 3.7 ± 1.1 | 78.4 ± 0.2 |
Homobutein | 2.8 ± 0.9 | -- | 82.6 1 |
α-TOH | 22.4 ± 5.8 | 2 2 | 77.1 3 |
Inhibition of Monophenolase Reaction (Substrate = l-Tyrosine) | ||||
Butein (µM) | Km or Kmapp (mM) | Vmax or Vmaxapp (µM/min) | KI′ (µM) Calc. from Vmax | KI′ (µM) Calc. from Km |
0 | 0.19 ± 0.01 | 3.85 ± 0.04 | - | - |
1.4 | 0.16 ± 0.02 | 3.24 ± 0.07 | 7.44 | 7.47 |
2.8 | 0.15 ± 0.01 | 3.02 ± 0.05 | 10.19 | 10.50 |
5.6 | 0.12 ± 0.02 | 2.21 ± 0.04 | 7.55 | 9.60 |
11.2 | 0.11 ± 0.01 | 1.95 ± 0.07 | 11.49 | 15.40 |
Average | 9.17 ± 2.01 | 10.74 ± 3.36 | ||
Inhibition of Diphenolase Reaction (Substrate = l-Dopa) | ||||
Butein (µM) | Km or Kmapp (mM) | Vmax or Vmaxapp (µM/min) | KI (µM) Competitive | KI′ (µM) Uncompetitive |
0 | 0.24 ± 0.01 | 11.78 ± 0.22 | - | - |
1.4 | 0.32 ± 0.01 | 10.93 ± 0.22 | 3.21 | 18.04 |
2.8 | 0.45 ± 0.06 | 10.60 ± 0.88 | 2.59 | 25.24 |
5.6 | 0.47 ± 0.02 | 8.17 ± 0.21 | 3.07 | 12.68 |
11.2 | 0.54 ± 0.03 | 7.42 ± 0.26 | 4.35 | 19.05 |
Average | 3.30 ± 0.75 | 18.75 ± 5.15 |
Inhibition of Monophenolase Reaction (Substrate = l-Tyrosine) | ||||
Homobutein (µM) | Km or Kmapp (mM) | Vmax or Vmaxapp (µM/min) | KI (µM) Competitive | KI′ (µM) Uncompetitive |
0 | 0.19 ± 0.01 | 3.85 ± 0.04 | - | - |
1.4 | 0.31 ± 0.01 | 3.83 ± 0.04 | 2.19 | 268.10 |
2.8 | 0.42 ± 0.02 | 3.78 ± 0.05 | 2.24 | 151.20 |
5.6 | 0.52 ± 0.02 | 3.63 ± 0.06 | 2.94 | 92.40 |
11.2 | 0.63 ± 0.01 | 3.15 ± 0.03 | 3.67 | 50.40 |
Average | 2.76 ± 0.70 | 140.53 ± 94.57 | ||
Inhibition of Diphenolase Reaction (Substrate = l-Dopa) | ||||
Homobutein (µM) | Km or Kmapp (mM) | Vmax or Vmaxapp (µM/min) | KI (µM) Competitive | KI′ (µM) Uncompetitive |
0 | 0.24 ± 0.01 | 11.60 ± 0.22 | - | - |
0.175 | 0.27 ± 0.01 | 11.48 ± 0.22 | 1.28 | 16.75 |
0.70 | 0.34 ± 0.05 | 11.30 ± 0.88 | 1.54 | 26.38 |
1.4 | 0.36 ± 0.02 | 11.10 ± 0.21 | 2.46 | 30.83 |
5.6 | 0.49 ± 0.08 | 10.84 ± 0.26 | 4.72 | 79.01 |
Average | 2.50 ± 1.56 | 38.24 ± 27.81 |
Butein IC50 (µM) | Homoutein IC50 (µM) | Kojic Acid IC50 (µM) | ||||
---|---|---|---|---|---|---|
Substrate (mM) | Monophenolase | Diphenolase | Monophenolase | Diphenolase | Monophenolase | Diphenolase |
0.05 | 45.05 ± 18.31 | 3.76 ± 0.96 | 4.01 ± 0.66 | 3.04 ± 0.84 | 15.51 ± 3.52 | 4.81 ± 0.52 |
0.125 | 35.60 ± 28.42 | 4.12 ± 1.39 | 4.58 ± 0.88 | 3.83 ± 0.94 | 18.64 ± 3.85 | 8.23 ± 1.05 |
0.25 | 12.87 ± 3.22 | 5.38 ± 0.90 | 6.06 ± 0.95 | 5.60 ± 1.07 | 20.52 ± 2.71 | 9.31 ± 1.75 |
0.50 | 12.26 ± 2.52 | 9.31 ± 0.85 | 8.75 ± 1.18 | 7.57 ± 1.11 | 24.91 ± 2.92 | 12.03 ± 2.12 |
1.00 | 10.88 ± 2.19 | 15.20 ± 1.25 | 14.78 ± 1.05 | 12.36 ± 2.00 | 33.14 ± 5.03 | 18.27 ± 3.42 |
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Pan, W.; Giovanardi, I.; Sagynova, T.; Cariola, A.; Bresciani, V.; Masetti, M.; Valgimigli, L. Potent Antioxidant and Anti-Tyrosinase Activity of Butein and Homobutein Probed by Molecular Kinetic and Mechanistic Studies. Antioxidants 2023, 12, 1763. https://doi.org/10.3390/antiox12091763
Pan W, Giovanardi I, Sagynova T, Cariola A, Bresciani V, Masetti M, Valgimigli L. Potent Antioxidant and Anti-Tyrosinase Activity of Butein and Homobutein Probed by Molecular Kinetic and Mechanistic Studies. Antioxidants. 2023; 12(9):1763. https://doi.org/10.3390/antiox12091763
Chicago/Turabian StylePan, Wenkai, Ilaria Giovanardi, Tomiris Sagynova, Alice Cariola, Veronica Bresciani, Matteo Masetti, and Luca Valgimigli. 2023. "Potent Antioxidant and Anti-Tyrosinase Activity of Butein and Homobutein Probed by Molecular Kinetic and Mechanistic Studies" Antioxidants 12, no. 9: 1763. https://doi.org/10.3390/antiox12091763