Design and Synthesis of (Z)-2-(Benzylamino)-5-benzylidenethiazol-4(5H)-one Derivatives as Tyrosinase Inhibitors and Their Anti-Melanogenic and Antioxidant Effects
Abstract
:1. Introduction
2. Results and Discussion
2.1. Chemistry
2.2. Mushroom Tyrosinase Inhibition of BABT Derivatives
2.3. Inhibitory Mechanisms of Derivatives 7 and 8 against Mushroom Tyrosinase
2.4. In Silico Docking Simulations of BABT Derivatives 7 and 8 with Various Tyrosinases
2.4.1. In Silico Docking Simulations of BABT Derivatives 7 and 8 with Mushroom Tyrosinase
2.4.2. Analysis of Molecular Dynamics Simulation
2.4.3. In Silico Docking Simulations of BABT Derivatives 7 and 8 with Human Tyrosinase
2.5. Cell Viabilities of BABT Derivatives 7 and 8 in B16F10 Cells
2.6. Effects of BABT Derivative 8 on Extracellular and Intracellular Melanin Production in B16F10 Cells
2.7. Effect of BABT Derivative 8 on Tyrosinase Activity in B16F10 Cells
2.8. Radical Scavenging Effects of BABT Derivatives 1–14 on 2,2-Diphenyl-1-Picrylhydrazyl (DPPH) and 2,2′-Azino-Bis(3-Ethylbenzothiazoline-6-Sulfonic Acid) (ABTS)
2.9. Scavenging Activities of BABT Derivatives against Reactive Oxygen Species (ROS) and Peroxynitrite
2.10. Effects of BABT Derivative 8 on the Expression Levels of Tyrosinase and Microphthalmia-associated Transcription Factor (MITF) Proteins
3. Materials and Methods
3.1. Chemistry
3.2. In Vitro Assays and In Silico and Kinetic Studies
3.2.1. Mushroom Tyrosinase Inhibition Assay
3.2.2. Kinetic Studies of the Efficacies of Derivatives 7 and 8 in Mushroom Tyrosinase Inhibition
3.2.3. In Silico Study of Chemical Interactions between Kojic Acid and Derivatives 7 and 8 and Mushroom Tyrosinase
3.2.4. Molecular Dynamics Simulation
3.2.5. In Silico Study of Chemical Interactions between Kojic Acid and Derivative 8 and the Human Tyrosinase Homology Model
3.2.6. Cell Culture
3.2.7. Cell Viability Assays
3.2.8. Measurement of Melanin Levels
3.2.9. Anti-Tyrosinase Activity Assay
3.2.10. DPPH Radical Scavenging Assay
3.2.11. ABTS Radical Scavenging Assay
3.2.12. SIN-1-Induced ROS Scavenging Assays
3.2.13. Peroxynitrite Scavenging Assays
3.2.14. Western Blotting Analysis of Tyrosinase and MITF Proteins
3.2.15. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Compd | R1 | R2 | R3 | R4 | IC50 (µM) a | |
---|---|---|---|---|---|---|
l-Tyrosine | l-Dopa | |||||
1 | H | H | OH | H | 27.5 ± 2.93 | 65.1 ± 8.29 |
2 | H | H | OMe | H | 125.5 ± 10.04 | 239.4 ± 2.38 |
3 | F | H | F | H | >300 | >300 |
4 | H | F | F | H | 288.7 ± 14.72 | >300 |
5 | H | OMe | OH | H | 148.3 ± 1.12 | >300 |
6 | H | OEt | OH | H | 198.9 ± 8.57 | 248.1 ± 11.54 |
7 | H | OH | OMe | H | 10.0 ± 0.90 | 10.3 ± 0.24 |
8 | OH | H | OH | H | 0.27 ± 0.03 | 1.04 ± 0.05 |
9 | H | OH | OH | H | >300 | >300 |
10 | OMe | H | OMe | H | 293.3 ± 13.12 | 213.6 ± 6.29 |
11 | H | OMe | OMe | H | >300 | >300 |
12 | H | OMe | OH | OMe | 166.0 ± 8.04 | >300 |
13 | H | t-Bu | OH | t-Bu | 136.7 ± 10.69 | >300 |
14 | H | OMe | OMe | OMe | 192.4 ± 9.04 | 231.1 ± 7.43 |
b KA | 28.6 ± 3.56 | 20.1 ± 0.46 |
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Lee, J.; Park, Y.J.; Jung, H.J.; Ullah, S.; Yoon, D.; Jeong, Y.; Kim, G.Y.; Kang, M.K.; Kang, D.; Park, Y.; et al. Design and Synthesis of (Z)-2-(Benzylamino)-5-benzylidenethiazol-4(5H)-one Derivatives as Tyrosinase Inhibitors and Their Anti-Melanogenic and Antioxidant Effects. Molecules 2023, 28, 848. https://doi.org/10.3390/molecules28020848
Lee J, Park YJ, Jung HJ, Ullah S, Yoon D, Jeong Y, Kim GY, Kang MK, Kang D, Park Y, et al. Design and Synthesis of (Z)-2-(Benzylamino)-5-benzylidenethiazol-4(5H)-one Derivatives as Tyrosinase Inhibitors and Their Anti-Melanogenic and Antioxidant Effects. Molecules. 2023; 28(2):848. https://doi.org/10.3390/molecules28020848
Chicago/Turabian StyleLee, Jieun, Yu Jung Park, Hee Jin Jung, Sultan Ullah, Dahye Yoon, Yeongmu Jeong, Ga Young Kim, Min Kyung Kang, Dongwan Kang, Yujin Park, and et al. 2023. "Design and Synthesis of (Z)-2-(Benzylamino)-5-benzylidenethiazol-4(5H)-one Derivatives as Tyrosinase Inhibitors and Their Anti-Melanogenic and Antioxidant Effects" Molecules 28, no. 2: 848. https://doi.org/10.3390/molecules28020848
APA StyleLee, J., Park, Y. J., Jung, H. J., Ullah, S., Yoon, D., Jeong, Y., Kim, G. Y., Kang, M. K., Kang, D., Park, Y., Chun, P., Chung, H. Y., & Moon, H. R. (2023). Design and Synthesis of (Z)-2-(Benzylamino)-5-benzylidenethiazol-4(5H)-one Derivatives as Tyrosinase Inhibitors and Their Anti-Melanogenic and Antioxidant Effects. Molecules, 28(2), 848. https://doi.org/10.3390/molecules28020848