Exploration of Compounds with 2-Phenylbenzo[d]oxazole Scaffold as Potential Skin-Lightening Agents through Inhibition of Melanin Biosynthesis and Tyrosinase Activity
Abstract
:1. Introduction
2. Results and Discussion
2.1. Preparation of Target Compounds, 2-Phenylbenzo[d]oxazoles 1–15
2.2. Mushroom Tyrosinase Inhibition of 2-Phenylbenzo[d]oxazole Compounds 1–15
2.3. Inhibition Mode of Action of 2-Phenylbenzoxazole Compounds
2.4. In Silico Docking Simulation of 2-Phenylbenoxazole Compounds 3, 8, and 13 and Mushroom Tyrosinase Using AutoDock Vina
2.5. Cytotoxicity in B16F10 Cells
2.6. Effect of 2-Phenylbenzoxazole Compounds 3, 8, and 13 on Melanogenesis in B16F10 Cells
2.7. Effect of 2-Phenylbenzoxazole Compounds 3, 8, and 13 on B16F10 Cellular Tyrosinase Inhibition
2.8. In Situ Tyrosinase Activity in B16F10 Cells
2.9. Cell Viability on HaCaT
2.10. In Vivo Depigmentation Effect of 2-Phenylbenzoxazole Compounds on Zebrafish Larvae
2.11. Antioxidant Ability of 2-Phenylbenzoxazole Compounds 1–15 Using 2,2-Diphenyl-1-picrylhydrazyl (DPPH), 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic Acid) (ABTS) Radical Cation, and Reactive Oxygen Species (ROS)
3. Materials and Methods
3.1. Synthesis
3.1.1. General Methods
3.1.2. Preparation of 2-Phenylbenzo[d]oxazole Compounds 1–15
General Synthetic Method for the Synthesis of 1 [40], 2 [41], 4, 6, 7, 9, 11 [25,42,43,44], 12 [41], and 14
General Synthetic Method for the Synthesis of 3, 5, 8, 10, 13 [45], and 15 (Supplementary Materials)
3.2. Reagents for Biological Experiments
3.3. Tyrosinase Activity Assay Using Mushroom Tyrosinase
3.4. Kinetic Study Experiment Using Mushroom Tyrosinase
3.5. Docking Simulation Using AutoDock Vina
3.6. Cell Culture
3.7. B16F10 Cell Viability Assay
3.8. Cellular Melanin Content Level Assay in B16F10 Cells
3.9. Cellular Tyrosinase Activity Assay in B16F10 Cells
3.10. In Situ Tyrosinase Activity Assay Using B16F10 Cells and l-dopa
3.11. HaCaT Cell Viability Assay
3.12. In Vivo Depigmentation Experiment Using Zebrafish Embryos
3.13. Measurement of Melanin Content and Tyrosinase Activity in Zebrafish Larvae
3.14. 2,2′-Diphenyl-1-picrylhydrazyl (DPPH) Radical Scavenging Assay
3.15. 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic Acid) (ABTS) Radical Cation Scavenging Assay
3.16. Reactive Oxygen Species (ROS) Scavenging Assay
3.17. Statistical Analysis
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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2-Phenylbenzo[d]oxazole compounds | |||||||
---|---|---|---|---|---|---|---|
Compd | R1 | R2 | R3 | R4 | R5 | IC50 Values (µM) | |
l-Tyrosine | l-Dopa | ||||||
1 | Me | H | H | H | OH | 152.51 ± 14.33 | >200 |
2 | Me | H | OMe | H | OMe | >200 | >200 |
3 | Me | H | OH | H | OH | 0.51 ± 0.00 | 16.78 ± 0.57 |
4 | Me | H | H | OH | OMe | >200 | >200 |
5 | Me | H | H | OH | OH | 144.06 ± 3.10 | 187.13 ± 30.28 |
6 | Cl | H | H | H | OH | 57.50 ± 8.78 | >200 |
7 | Cl | H | OMe | H | OMe | >200 | >200 |
8 | Cl | H | OH | H | OH | 2.22 ± 0.16 | 20.38 ± 1.99 |
9 | Cl | H | H | OH | OMe | >200 | >200 |
10 | Cl | H | H | OH | OH | 59.02 ± 4.74 | >200 |
11 | H | Me | H | H | OH | 76.80 ± 3.84 | >200 |
12 | H | Me | OMe | H | OMe | >200 | >200 |
13 | H | Me | OH | H | OH | 3.50 ± 0.07 | 20.76 ± 1.02 |
14 | H | Me | H | OH | OMe | 146.24 ± 16.40 | >200 |
15 | H | Me | H | OH | OH | 80.29 ± 5.24 | >200 |
KA a | 14.33 ± 1.63 | 40.42 ± 3.70 |
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Jung, H.J.; Park, H.S.; Park, H.S.; Kim, H.J.; Yoon, D.; Park, Y.; Chun, P.; Chung, H.Y.; Moon, H.R. Exploration of Compounds with 2-Phenylbenzo[d]oxazole Scaffold as Potential Skin-Lightening Agents through Inhibition of Melanin Biosynthesis and Tyrosinase Activity. Molecules 2024, 29, 4162. https://doi.org/10.3390/molecules29174162
Jung HJ, Park HS, Park HS, Kim HJ, Yoon D, Park Y, Chun P, Chung HY, Moon HR. Exploration of Compounds with 2-Phenylbenzo[d]oxazole Scaffold as Potential Skin-Lightening Agents through Inhibition of Melanin Biosynthesis and Tyrosinase Activity. Molecules. 2024; 29(17):4162. https://doi.org/10.3390/molecules29174162
Chicago/Turabian StyleJung, Hee Jin, Hyeon Seo Park, Hye Soo Park, Hye Jin Kim, Dahye Yoon, Yujin Park, Pusoon Chun, Hae Young Chung, and Hyung Ryong Moon. 2024. "Exploration of Compounds with 2-Phenylbenzo[d]oxazole Scaffold as Potential Skin-Lightening Agents through Inhibition of Melanin Biosynthesis and Tyrosinase Activity" Molecules 29, no. 17: 4162. https://doi.org/10.3390/molecules29174162