Hydroxyketone Tyrosinase Inhibitors: Mechanism of Action, Applications and Perspectives in Depigmentation and Melanoma Therapy
Abstract
1. Introduction
The Role of Ketone and Hydroxyl Groups
2. Results
HOMO–LUMO Transition and Biological Activity
3. Materials and Methods
4. Conclusions
- Designing new tyrosinase inhibitors with better pharmacokinetic and pharmacodynamic properties.
- Studying the mechanisms of action of tyrosinase inhibitors at the molecular and cellular level.
- Evaluating the efficacy of combinations of tyrosinase inhibitors with other anticancer therapies, such as immunotherapy and targeted therapies.
- Identifying biomarkers that will predict patient response to tyrosinase inhibitors.
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compound | FlexX Docking Score (Human Tyrosinase-Related Protein 1—PDB 5M8M) | |
---|---|---|
1 | H | −18.3830 |
2 | 2-CH3 | −11.4455 |
3 | 3-CH3 | −18.1416 |
4 | 4-CH3 | −20.6370 |
5 | 2-CH3O | −19.2495 |
6 | 3-CH3O | −21.8964 |
7 | 4-CH3O | −21.2831 |
8 | 2-Cl | −18.2830 |
9 | 3-Cl | −18.6898 |
10 | 4-Cl | −19.0834 |
11 | 2-F | −21.6780 |
12 | 3-F | −23.5156 |
13 | 4-F | −20.9563 |
Kojic acid | −16.5135 | |
Tropolone | −11.7053 |
Complex | ΔG | Van der Waal Energy | Electrostatic Energy | Polar Solvation Energy | Non-Polar Solvation Energy | Solvation Energy |
---|---|---|---|---|---|---|
5M8M- kojic acid | −13.41 ± 2.92 | −23.37 ± 2.03 | −5.41 ± 2.04 | 15.37 ± 3.31 | −1.84 ± 0.04 | 15.36 ± 3.31 |
5M8M- Compound 12 | −15.80 ± 3.10 | −25.70 ± 2.10 | −7.00 ± 2.10 | 18.60 ± 3.40 | 2.00 ± 0.08 | 16.60 ± 3.40 |
5M8M- Tropolone | −11.50 ± 2.20 | −20.20 ± 2.00 | −3.40 ± 1.90 | 13.40 ± 2.50 | −1.60 ± 0.26 | 11.80 ± 2.50 |
Compound | E_HOMO (a.u.) | E_LUMO (a.u.) | ΔE (a.u.) | η (a.u.) | I (a.u.) | A (a.u.) | χ (a.u.) | ω (a.u.) |
---|---|---|---|---|---|---|---|---|
1 | −0.22417 | −0.06247 | 0.1617 | 0.08085 | 0.22417 | 0.06247 | 0.14332 | 0.12704 |
2 | −0.2058 | −0.0588 | 0.147 | 0.0735 | 0.2058 | 0.0588 | 0.1323 | 0.11907 |
3 | −0.2205 | −0.06247 | 0.15802 | 0.07901 | 0.2205 | 0.06247 | 0.14148 | 0.12668 |
4 | −0.2205 | −0.05512 | 0.16537 | 0.08269 | 0.2205 | 0.05512 | 0.13781 | 0.11484 |
5 | −0.20947 | −0.0588 | 0.15067 | 0.07534 | 0.20947 | 0.0588 | 0.13413 | 0.11941 |
6 | −0.21682 | −0.06615 | 0.15067 | 0.07534 | 0.21682 | 0.06615 | 0.14148 | 0.13286 |
7 | −0.21682 | −0.04777 | 0.16905 | 0.08452 | 0.21682 | 0.04777 | 0.1323 | 0.10354 |
8 | −0.22785 | −0.06615 | 0.1617 | 0.08085 | 0.22785 | 0.06615 | 0.147 | 0.13363 |
9 | −0.22785 | −0.06982 | 0.18375 | 0.09187 | 0.22785 | 0.06982 | 0.14883 | 0.12056 |
10 | −0.22417 | −0.06247 | 0.1617 | 0.08085 | 0.22417 | 0.06247 | 0.14332 | 0.12704 |
11 | −0.21315 | −0.06247 | 0.15067 | 0.07534 | 0.21315 | 0.06247 | 0.13781 | 0.12605 |
12 | −0.21682 | −0.06247 | 0.15435 | 0.07717 | 0.21682 | 0.06247 | 0.13965 | 0.12635 |
13 | −0.2205 | −0.0588 | 0.1617 | 0.08085 | 0.2205 | 0.0588 | 0.13965 | 0.1206 |
Kojic acid | −0.23152 | −0.04042 | 0.15435 | 0.07717 | 0.23152 | 0.04042 | 0.13597 | 0.11979 |
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Bogdańska, B.; Khylyuk, D.; Matosiuk, D. Hydroxyketone Tyrosinase Inhibitors: Mechanism of Action, Applications and Perspectives in Depigmentation and Melanoma Therapy. Molecules 2025, 30, 4079. https://doi.org/10.3390/molecules30204079
Bogdańska B, Khylyuk D, Matosiuk D. Hydroxyketone Tyrosinase Inhibitors: Mechanism of Action, Applications and Perspectives in Depigmentation and Melanoma Therapy. Molecules. 2025; 30(20):4079. https://doi.org/10.3390/molecules30204079
Chicago/Turabian StyleBogdańska, Barbara, Dmytro Khylyuk, and Dariusz Matosiuk. 2025. "Hydroxyketone Tyrosinase Inhibitors: Mechanism of Action, Applications and Perspectives in Depigmentation and Melanoma Therapy" Molecules 30, no. 20: 4079. https://doi.org/10.3390/molecules30204079
APA StyleBogdańska, B., Khylyuk, D., & Matosiuk, D. (2025). Hydroxyketone Tyrosinase Inhibitors: Mechanism of Action, Applications and Perspectives in Depigmentation and Melanoma Therapy. Molecules, 30(20), 4079. https://doi.org/10.3390/molecules30204079