Design, Synthesis, and Antioxidant and Anti-Tyrosinase Activities of (<i>Z</i>)-5-Benzylidene-2-(naphthalen-1-ylamino)thiazol-4(5<i>H</i>)-one Analogs: In Vitro and In Vivo Insights
Fifteen compounds (<b>1</b>–<b>15</b>) constructed on a hybrid structure combining a β-phenyl-α,β-unsaturated carbonyl template and a 2-aminothiazol-4(5<i>H</i>)-one scaffold were designed and synthesized as potential novel anti-tyrosinase substances. Two compound...
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2025-01-01
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| author | Hee Jin Jung Hye Jin Kim Hyeon Seo Park Hye Soo Park Jeongin Ko Dahye Yoon Yujin Park Pusoon Chun Hae Young Chung Hyung Ryong Moon |
| author_facet | Hee Jin Jung Hye Jin Kim Hyeon Seo Park Hye Soo Park Jeongin Ko Dahye Yoon Yujin Park Pusoon Chun Hae Young Chung Hyung Ryong Moon |
| author_sort | Hee Jin Jung |
| collection | DOAJ |
| description | Fifteen compounds (<b>1</b>–<b>15</b>) constructed on a hybrid structure combining a β-phenyl-α,β-unsaturated carbonyl template and a 2-aminothiazol-4(5<i>H</i>)-one scaffold were designed and synthesized as potential novel anti-tyrosinase substances. Two compounds (<b>10</b> and <b>15</b>) showed more potent inhibition against mushroom tyrosinase than kojic acid, and the inhibitory activity of <b>10</b> (IC<sub>50</sub> value: 1.60 μM) was 11 times stronger than that of kojic acid. Lineweaver–Burk plots indicated that these two compounds were competitive inhibitors that bound to the mushroom tyrosinase active site, which was supported by in silico experiments. Compound <b>10</b> was an anti-tyrosinase and anti-melanogenic substance in B16F10 cells and was more potent than kojic acid, without cytotoxicity. Compound <b>15</b> exhibited the most potent effect on zebrafish larval depigmentation and showed a depigmentation effect comparable to kojic acid, even at a concentration 200 times lower. Compounds <b>8</b> and <b>10</b> exhibited strong antioxidant capacities, scavenging 2,2-diphenyl-1-picrylhydrazyl, (2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid)<sup>+</sup> radicals, and reactive oxygen species. Hybrid compounds <b>10</b> and <b>15</b> are potential therapeutic agents for skin hyperpigmentation disorders. |
| format | Article |
| id | doaj-art-7e0eb5f4d7b14ec999cb0b316b4d055f |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-7e0eb5f4d7b14ec999cb0b316b4d055f2025-01-24T13:43:26ZengMDPI AGMolecules1420-30492025-01-0130228910.3390/molecules30020289Design, Synthesis, and Antioxidant and Anti-Tyrosinase Activities of (<i>Z</i>)-5-Benzylidene-2-(naphthalen-1-ylamino)thiazol-4(5<i>H</i>)-one Analogs: In Vitro and In Vivo InsightsHee Jin Jung0Hye Jin Kim1Hyeon Seo Park2Hye Soo Park3Jeongin Ko4Dahye Yoon5Yujin Park6Pusoon Chun7Hae Young Chung8Hyung Ryong Moon9Department 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 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 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 KoreaFifteen compounds (<b>1</b>–<b>15</b>) constructed on a hybrid structure combining a β-phenyl-α,β-unsaturated carbonyl template and a 2-aminothiazol-4(5<i>H</i>)-one scaffold were designed and synthesized as potential novel anti-tyrosinase substances. Two compounds (<b>10</b> and <b>15</b>) showed more potent inhibition against mushroom tyrosinase than kojic acid, and the inhibitory activity of <b>10</b> (IC<sub>50</sub> value: 1.60 μM) was 11 times stronger than that of kojic acid. Lineweaver–Burk plots indicated that these two compounds were competitive inhibitors that bound to the mushroom tyrosinase active site, which was supported by in silico experiments. Compound <b>10</b> was an anti-tyrosinase and anti-melanogenic substance in B16F10 cells and was more potent than kojic acid, without cytotoxicity. Compound <b>15</b> exhibited the most potent effect on zebrafish larval depigmentation and showed a depigmentation effect comparable to kojic acid, even at a concentration 200 times lower. Compounds <b>8</b> and <b>10</b> exhibited strong antioxidant capacities, scavenging 2,2-diphenyl-1-picrylhydrazyl, (2,2-azino-bis-3-ethylbenzothiazoline-6-sulphonic acid)<sup>+</sup> radicals, and reactive oxygen species. Hybrid compounds <b>10</b> and <b>15</b> are potential therapeutic agents for skin hyperpigmentation disorders.https://www.mdpi.com/1420-3049/30/2/289tyrosinasezebrafish larvamelanindepigmentationkojic acidB16F10 cells |
| spellingShingle | Hee Jin Jung Hye Jin Kim Hyeon Seo Park Hye Soo Park Jeongin Ko Dahye Yoon Yujin Park Pusoon Chun Hae Young Chung Hyung Ryong Moon Design, Synthesis, and Antioxidant and Anti-Tyrosinase Activities of (<i>Z</i>)-5-Benzylidene-2-(naphthalen-1-ylamino)thiazol-4(5<i>H</i>)-one Analogs: In Vitro and In Vivo Insights Molecules tyrosinase zebrafish larva melanin depigmentation kojic acid B16F10 cells |
| title | Design, Synthesis, and Antioxidant and Anti-Tyrosinase Activities of (<i>Z</i>)-5-Benzylidene-2-(naphthalen-1-ylamino)thiazol-4(5<i>H</i>)-one Analogs: In Vitro and In Vivo Insights |
| title_full | Design, Synthesis, and Antioxidant and Anti-Tyrosinase Activities of (<i>Z</i>)-5-Benzylidene-2-(naphthalen-1-ylamino)thiazol-4(5<i>H</i>)-one Analogs: In Vitro and In Vivo Insights |
| title_fullStr | Design, Synthesis, and Antioxidant and Anti-Tyrosinase Activities of (<i>Z</i>)-5-Benzylidene-2-(naphthalen-1-ylamino)thiazol-4(5<i>H</i>)-one Analogs: In Vitro and In Vivo Insights |
| title_full_unstemmed | Design, Synthesis, and Antioxidant and Anti-Tyrosinase Activities of (<i>Z</i>)-5-Benzylidene-2-(naphthalen-1-ylamino)thiazol-4(5<i>H</i>)-one Analogs: In Vitro and In Vivo Insights |
| title_short | Design, Synthesis, and Antioxidant and Anti-Tyrosinase Activities of (<i>Z</i>)-5-Benzylidene-2-(naphthalen-1-ylamino)thiazol-4(5<i>H</i>)-one Analogs: In Vitro and In Vivo Insights |
| title_sort | design synthesis and antioxidant and anti tyrosinase activities of i z i 5 benzylidene 2 naphthalen 1 ylamino thiazol 4 5 i h i one analogs in vitro and in vivo insights |
| topic | tyrosinase zebrafish larva melanin depigmentation kojic acid B16F10 cells |
| url | https://www.mdpi.com/1420-3049/30/2/289 |
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