Design and Synthesis of Novel 6-(Substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-<i>d</i>]thiazole Compounds as Tyrosinase Inhibitors: In Vitro and In Vivo Insights
The 2,4-dihydroxyphenyl group is commonly present in the chemical structures of potent tyrosinase inhibitors. Based on this observation, a series of 6-(substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-<i data-eusoft-scrollable-element="1">d</i>]thiazole compounds <b data...
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2025-03-01
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| author | Hyeon Seo Park Hee Jin Jung Hye Soo Park Hye Jin Kim Sang Gyun Noh Yujin Park Pusoon Chun Hae Young Chung Hyung Ryong Moon |
| author_facet | Hyeon Seo Park Hee Jin Jung Hye Soo Park Hye Jin Kim Sang Gyun Noh Yujin Park Pusoon Chun Hae Young Chung Hyung Ryong Moon |
| author_sort | Hyeon Seo Park |
| collection | DOAJ |
| description | The 2,4-dihydroxyphenyl group is commonly present in the chemical structures of potent tyrosinase inhibitors. Based on this observation, a series of 6-(substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-<i data-eusoft-scrollable-element="1">d</i>]thiazole compounds <b data-eusoft-scrollable-element="1">1</b>–<b data-eusoft-scrollable-element="1">13</b> were designed and synthesized as potential tyrosinase inhibitors. Among these, compounds <b data-eusoft-scrollable-element="1">5</b> and <b data-eusoft-scrollable-element="1">9</b> strongly inhibited mushroom tyrosinase activity. Particularly, compound <b data-eusoft-scrollable-element="1">9</b> exhibited nanomolar IC<sub data-eusoft-scrollable-element="1">50</sub> values regardless of the substrate used, whereas kojic acid yielded IC<sub data-eusoft-scrollable-element="1">50</sub> values of 15.99–26.18 μM. Kinetic studies on mushroom tyrosinase revealed that compounds <b data-eusoft-scrollable-element="1">5</b> and <b data-eusoft-scrollable-element="1">9</b> competitively inhibited tyrosinase activity, findings further corroborated by in silico docking analysis. In B16F10 cell-based experiments, both compounds effectively inhibited the cellular tyrosinase activity and melanin formation. These inhibitory effects were confirmed through in situ cellular tyrosinase activity assays. Compound <b data-eusoft-scrollable-element="1">9</b> exhibited strong antioxidant activity by scavenging radicals, suggesting that its ability to reduce melanin production may be attributed to a combination of its antioxidant and tyrosinase inhibitory properties. Additionally, five compounds, including compound <b data-eusoft-scrollable-element="1">5</b>, demonstrated effective depigmentation activity in vivo in zebrafish embryos, and their depigmentation efficacy was similar to that of kojic acid, even at concentrations hundreds of times lower. These findings suggest that 6-(substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-<i data-eusoft-scrollable-element="1">d</i>]thiazole compounds may be promising anti-melanogenic agents. |
| format | Article |
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| spelling | doaj-art-fa13e46723f5493a8958ea9d50bf3dc72025-08-20T02:15:58ZengMDPI AGMolecules1420-30492025-03-01307153510.3390/molecules30071535Design and Synthesis of Novel 6-(Substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-<i>d</i>]thiazole Compounds as Tyrosinase Inhibitors: In Vitro and In Vivo InsightsHyeon Seo Park0Hee Jin Jung1Hye Soo Park2Hye Jin Kim3Sang Gyun Noh4Yujin Park5Pusoon Chun6Hae Young Chung7Hyung Ryong Moon8Department of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of KoreaDepartment of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of KoreaDepartment of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of KoreaDepartment of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of KoreaDepartment of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of KoreaDepartment of Medicinal Chemistry, New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, Republic of KoreaCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, Gimhae 50834, Republic of KoreaDepartment of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of KoreaDepartment of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of KoreaThe 2,4-dihydroxyphenyl group is commonly present in the chemical structures of potent tyrosinase inhibitors. Based on this observation, a series of 6-(substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-<i data-eusoft-scrollable-element="1">d</i>]thiazole compounds <b data-eusoft-scrollable-element="1">1</b>–<b data-eusoft-scrollable-element="1">13</b> were designed and synthesized as potential tyrosinase inhibitors. Among these, compounds <b data-eusoft-scrollable-element="1">5</b> and <b data-eusoft-scrollable-element="1">9</b> strongly inhibited mushroom tyrosinase activity. Particularly, compound <b data-eusoft-scrollable-element="1">9</b> exhibited nanomolar IC<sub data-eusoft-scrollable-element="1">50</sub> values regardless of the substrate used, whereas kojic acid yielded IC<sub data-eusoft-scrollable-element="1">50</sub> values of 15.99–26.18 μM. Kinetic studies on mushroom tyrosinase revealed that compounds <b data-eusoft-scrollable-element="1">5</b> and <b data-eusoft-scrollable-element="1">9</b> competitively inhibited tyrosinase activity, findings further corroborated by in silico docking analysis. In B16F10 cell-based experiments, both compounds effectively inhibited the cellular tyrosinase activity and melanin formation. These inhibitory effects were confirmed through in situ cellular tyrosinase activity assays. Compound <b data-eusoft-scrollable-element="1">9</b> exhibited strong antioxidant activity by scavenging radicals, suggesting that its ability to reduce melanin production may be attributed to a combination of its antioxidant and tyrosinase inhibitory properties. Additionally, five compounds, including compound <b data-eusoft-scrollable-element="1">5</b>, demonstrated effective depigmentation activity in vivo in zebrafish embryos, and their depigmentation efficacy was similar to that of kojic acid, even at concentrations hundreds of times lower. These findings suggest that 6-(substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-<i data-eusoft-scrollable-element="1">d</i>]thiazole compounds may be promising anti-melanogenic agents.https://www.mdpi.com/1420-3049/30/7/1535melanintyrosinase2,4-dihydroxyphenylzebrafish embryosdepigmentation |
| spellingShingle | Hyeon Seo Park Hee Jin Jung Hye Soo Park Hye Jin Kim Sang Gyun Noh Yujin Park Pusoon Chun Hae Young Chung Hyung Ryong Moon Design and Synthesis of Novel 6-(Substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-<i>d</i>]thiazole Compounds as Tyrosinase Inhibitors: In Vitro and In Vivo Insights Molecules melanin tyrosinase 2,4-dihydroxyphenyl zebrafish embryos depigmentation |
| title | Design and Synthesis of Novel 6-(Substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-<i>d</i>]thiazole Compounds as Tyrosinase Inhibitors: In Vitro and In Vivo Insights |
| title_full | Design and Synthesis of Novel 6-(Substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-<i>d</i>]thiazole Compounds as Tyrosinase Inhibitors: In Vitro and In Vivo Insights |
| title_fullStr | Design and Synthesis of Novel 6-(Substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-<i>d</i>]thiazole Compounds as Tyrosinase Inhibitors: In Vitro and In Vivo Insights |
| title_full_unstemmed | Design and Synthesis of Novel 6-(Substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-<i>d</i>]thiazole Compounds as Tyrosinase Inhibitors: In Vitro and In Vivo Insights |
| title_short | Design and Synthesis of Novel 6-(Substituted phenyl)-[1,3]dioxolo[4′,5′:4,5]benzo[1,2-<i>d</i>]thiazole Compounds as Tyrosinase Inhibitors: In Vitro and In Vivo Insights |
| title_sort | design and synthesis of novel 6 substituted phenyl 1 3 dioxolo 4 5 4 5 benzo 1 2 i d i thiazole compounds as tyrosinase inhibitors in vitro and in vivo insights |
| topic | melanin tyrosinase 2,4-dihydroxyphenyl zebrafish embryos depigmentation |
| url | https://www.mdpi.com/1420-3049/30/7/1535 |
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