Design and Synthesis of Novel 6-(Substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]thiazole Compounds as Tyrosinase Inhibitors: In Vitro and In Vivo Insights
Abstract
:1. Introduction
2. Results and Discussion
2.1. Preparation of Target Compounds, 6-(substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]thiazole 1–13
2.2. Mushroom Tyrosinase-Inhibitory Activity of Target Compounds 1–13
2.3. Kinetic Study on Mushroom Tyrosinase Through Analyzing Lineweaver–Burk Plots
2.4. Docking Simulation of Mushroom Tyrosinase and Compounds 5 and 9
2.5. Cell Viability of Compounds 5 and 9 on B16F10 Cells
2.6. Effects of Compounds 5 and 9 on B16F10 Cellular Tyrosinase Activity
2.7. Effects of Compounds 5 and 9 on Melanogenesis in B16F10 Cells
2.8. Effects of Compounds 5 and 9 on In Situ B16F10 Cell Tyrosinase Inhibition
2.9. Antioxidant Effects of Compounds 5 and 9 on 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ATBS)+ Radicals
2.10. Depigmentation Effect of Compounds on Zebrafish Larvae
2.11. Cell Viability of Compounds 5 and 9 on HaCaT Cells
3. Materials and Methods
3.1. Synthesis
General Methods
3.2. Mushroom Tyrosinase Inhibitory Activity Assay [59,60]
3.3. Kinetic Analysis of Mushroom Tyrosinase with Compound 5 or 9 [61,62]
3.4. In Silico Docking Simulations of Compounds 5 and 9 Against Mushroom Tyrosinase [63]
3.5. Cell Culture
3.6. Cytotoxicity Assay on HaCaT and B16F10 Cells [64,65]
3.7. Cellular Tyrosinase Activity Assay Using B16F10 Cells [66]
3.8. Cellular Melanin Content Assay Using B16F10 Cells [66]
3.9. In Situ Cellular Tyrosinase Activity Assay Using B16F10 Cells [67,68]
3.10. Scavenging Assay for ABTS•+ [69]
3.11. Scavenging Assay for DPPH Radicals [70,71]
3.12. In Vivo Pigmentation Assay Using Zebrafish Embryos [72,73]
3.13. 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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Cpd | R1 | R2 | R3 | R4 | IC50 (μM, Mean ± SEM) a /Inhibition (%, Mean ± SEM) b at 50 μM | |
---|---|---|---|---|---|---|
l-Dopa | l-Tyrosine | |||||
1 | H | OCH3 | OH | H | ND c/1.71 ± 0.36 | ND/25.90 ± 1.51 |
2 | H | OEt | OH | H | 49.73 ± 2.77/50.33 ± 2.04 | ND/14.90 ± 0.76 |
3 | H | H | OCH3 | H | ND/17.19 ± 3.09 | ND/11.05 ± 0.82 |
4 | H | OH | OCH3 | H | 40.89 ± 3.57/63.04 ± 5.54 | ND/25.52 ± 2.57 |
5 | H | H | OH | H | 36.12 ± 2.17/63.28 ± 3.14 | 34.21 ± 0.68/61.39 ± 0.65 |
6 | H | Br | OH | H | ND/27.94 ± 0.78 | ND/17.0 ± 2.36 |
7 | H | Br | OH | Br | ND/29.70 ± 0.39 | ND/17.72 ± 1.10 |
8 | H | OH | OH | H | ND/18.61 ± 1.38 | ND/4.95 ± 0.63 |
9 | OH | H | OH | H | 0.74 ± 0.03/76.11 ± 0.41 d | 0.24 ± 0.00/71.76 ± 0.11 e |
10 | H | OCH3 | OH | OCH3 | 50.13 ± 8.65/53.20 ± 8.09 | ND/0.54 ± 0.16 |
11 | H | OCH3 | OCH3 | H | ND/19.45 ± 0.35 | ND/0.82 ± 0.05 |
12 | OCH3 | H | OCH3 | H | ND/32.77 ± 1.69 | ND/10.63 ± 1.53 |
13 | H | OCH3 | OCH3 | OCH3 | ND/4.99 ± 1.93 | ND/16.56 ± 3.62 |
KA f | 26.18 ± 1.34/74.09 ± 2.32 | 15.99 ± 0.72/90.83 ± 0.63 |
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Park, H.S.; Jung, H.J.; Park, H.S.; Kim, H.J.; Noh, S.G.; Park, Y.; Chun, P.; Chung, H.Y.; Moon, H.R. Design and Synthesis of Novel 6-(Substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]thiazole Compounds as Tyrosinase Inhibitors: In Vitro and In Vivo Insights. Molecules 2025, 30, 1535. https://doi.org/10.3390/molecules30071535
Park HS, Jung HJ, Park HS, Kim HJ, Noh SG, Park Y, Chun P, Chung HY, Moon HR. Design and Synthesis of Novel 6-(Substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]thiazole Compounds as Tyrosinase Inhibitors: In Vitro and In Vivo Insights. Molecules. 2025; 30(7):1535. https://doi.org/10.3390/molecules30071535
Chicago/Turabian StylePark, Hyeon Seo, Hee Jin Jung, Hye Soo Park, Hye Jin Kim, Sang Gyun Noh, Yujin Park, Pusoon Chun, Hae Young Chung, and Hyung Ryong Moon. 2025. "Design and Synthesis of Novel 6-(Substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]thiazole Compounds as Tyrosinase Inhibitors: In Vitro and In Vivo Insights" Molecules 30, no. 7: 1535. https://doi.org/10.3390/molecules30071535
APA StylePark, H. S., Jung, H. J., Park, H. S., Kim, H. J., Noh, S. G., Park, Y., Chun, P., Chung, H. Y., & Moon, H. R. (2025). Design and Synthesis of Novel 6-(Substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-d]thiazole Compounds as Tyrosinase Inhibitors: In Vitro and In Vivo Insights. Molecules, 30(7), 1535. https://doi.org/10.3390/molecules30071535