Design, Synthesis, In Vitro, and In Silico Insights of 5-(Substituted benzylidene)-2-phenylthiazol-4(5<i>H</i>)-one Derivatives: A Novel Class of Anti-Melanogenic Compounds
(<i>Z</i>)-5-Benzylidene-2-phenylthiazol-4(5<i>H</i>)-one ((<i>Z</i>)-BPT) derivatives were designed by combining the structural characteristics of two tyrosinase inhibitors. The double-bond geometry of trisubstituted alkenes, (<i>Z</i>)-BPTs <b>...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-04-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/8/3293 |
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| author | Dahye Yoon Min Kyung Kang Hee Jin Jung Sultan Ullah Jieun Lee Yeongmu Jeong Sang Gyun Noh Dongwan Kang Yujin Park Pusoon Chun Hae Young Chung Hyung Ryong Moon |
| author_facet | Dahye Yoon Min Kyung Kang Hee Jin Jung Sultan Ullah Jieun Lee Yeongmu Jeong Sang Gyun Noh Dongwan Kang Yujin Park Pusoon Chun Hae Young Chung Hyung Ryong Moon |
| author_sort | Dahye Yoon |
| collection | DOAJ |
| description | (<i>Z</i>)-5-Benzylidene-2-phenylthiazol-4(5<i>H</i>)-one ((<i>Z</i>)-BPT) derivatives were designed by combining the structural characteristics of two tyrosinase inhibitors. The double-bond geometry of trisubstituted alkenes, (<i>Z</i>)-BPTs <b>1</b>–<b>14</b>, was determined based on the <sup>3</sup><i>J</i><sub>C,Hβ</sub> coupling constant of <sup>1</sup>H-coupled <sup>13</sup>C NMR spectra. Three (<i>Z</i>)-BPT derivatives (<b>1</b>–<b>3</b>) showed stronger tyrosinase inhibitory activities than kojic acid; in particular, <b>2</b> was to be 189-fold more potent than kojic acid. Kinetic analysis using mushroom tyrosinase indicated that <b>1</b> and <b>2</b> were competitive inhibitors, whereas <b>3</b> was a mixed-type inhibitor. The in silico results revealed that <b>1</b>–<b>3</b> could strongly bind to the active sites of mushroom and human tyrosinases, supporting the kinetic results. Derivatives <b>1</b> and <b>2</b> decreased the intracellular melanin contents in a concentration-dependent manner in B16F10 cells, and their anti-melanogenic efficacy exceeded that of kojic acid. The anti-tyrosinase activity of <b>1</b> and <b>2</b> in B16F10 cells was similar to their anti-melanogenic effects, suggesting that their anti-melanogenic effects were primarily owing to their anti-tyrosinase activity. Western blotting of B16F10 cells revealed that the derivatives <b>1</b> and <b>2</b> inhibited tyrosinase expression, which partially contributes to their anti-melanogenic ability. Several derivatives, including <b>2</b> and <b>3</b>, exhibited potent antioxidant activities against ABTS cation radicals, DPPH radicals, ROS, and peroxynitrite. These results suggest that (<i>Z</i>)-BPT derivatives <b>1</b> and <b>2</b> have promising potential as novel anti-melanogenic agents. |
| first_indexed | 2024-03-11T04:42:40Z |
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| id | doaj.art-83de3ac4d88c40939741c8536066e95e |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T04:42:40Z |
| publishDate | 2023-04-01 |
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| series | Molecules |
| spelling | doaj.art-83de3ac4d88c40939741c8536066e95e2023-11-17T20:36:57ZengMDPI AGMolecules1420-30492023-04-01288329310.3390/molecules28083293Design, Synthesis, In Vitro, and In Silico Insights of 5-(Substituted benzylidene)-2-phenylthiazol-4(5<i>H</i>)-one Derivatives: A Novel Class of Anti-Melanogenic CompoundsDahye Yoon0Min Kyung Kang1Hee Jin Jung2Sultan Ullah3Jieun Lee4Yeongmu Jeong5Sang Gyun Noh6Dongwan Kang7Yujin Park8Pusoon Chun9Hae Young Chung10Hyung Ryong Moon11Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of KoreaDepartment of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of KoreaDepartment of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of KoreaDepartment of Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USADepartment of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of KoreaDepartment of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of KoreaDepartment of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of KoreaDepartment of Medicinal Chemistry, New Drug Development Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu 41061, 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, Pusan National University, Busan 46241, Republic of KoreaDepartment of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Republic of Korea(<i>Z</i>)-5-Benzylidene-2-phenylthiazol-4(5<i>H</i>)-one ((<i>Z</i>)-BPT) derivatives were designed by combining the structural characteristics of two tyrosinase inhibitors. The double-bond geometry of trisubstituted alkenes, (<i>Z</i>)-BPTs <b>1</b>–<b>14</b>, was determined based on the <sup>3</sup><i>J</i><sub>C,Hβ</sub> coupling constant of <sup>1</sup>H-coupled <sup>13</sup>C NMR spectra. Three (<i>Z</i>)-BPT derivatives (<b>1</b>–<b>3</b>) showed stronger tyrosinase inhibitory activities than kojic acid; in particular, <b>2</b> was to be 189-fold more potent than kojic acid. Kinetic analysis using mushroom tyrosinase indicated that <b>1</b> and <b>2</b> were competitive inhibitors, whereas <b>3</b> was a mixed-type inhibitor. The in silico results revealed that <b>1</b>–<b>3</b> could strongly bind to the active sites of mushroom and human tyrosinases, supporting the kinetic results. Derivatives <b>1</b> and <b>2</b> decreased the intracellular melanin contents in a concentration-dependent manner in B16F10 cells, and their anti-melanogenic efficacy exceeded that of kojic acid. The anti-tyrosinase activity of <b>1</b> and <b>2</b> in B16F10 cells was similar to their anti-melanogenic effects, suggesting that their anti-melanogenic effects were primarily owing to their anti-tyrosinase activity. Western blotting of B16F10 cells revealed that the derivatives <b>1</b> and <b>2</b> inhibited tyrosinase expression, which partially contributes to their anti-melanogenic ability. Several derivatives, including <b>2</b> and <b>3</b>, exhibited potent antioxidant activities against ABTS cation radicals, DPPH radicals, ROS, and peroxynitrite. These results suggest that (<i>Z</i>)-BPT derivatives <b>1</b> and <b>2</b> have promising potential as novel anti-melanogenic agents.https://www.mdpi.com/1420-3049/28/8/3293(<i>Z</i>)-BPT derivativestyrosinasemelanogenesiskojic acidantioxidantin silico |
| spellingShingle | Dahye Yoon Min Kyung Kang Hee Jin Jung Sultan Ullah Jieun Lee Yeongmu Jeong Sang Gyun Noh Dongwan Kang Yujin Park Pusoon Chun Hae Young Chung Hyung Ryong Moon Design, Synthesis, In Vitro, and In Silico Insights of 5-(Substituted benzylidene)-2-phenylthiazol-4(5<i>H</i>)-one Derivatives: A Novel Class of Anti-Melanogenic Compounds Molecules (<i>Z</i>)-BPT derivatives tyrosinase melanogenesis kojic acid antioxidant in silico |
| title | Design, Synthesis, In Vitro, and In Silico Insights of 5-(Substituted benzylidene)-2-phenylthiazol-4(5<i>H</i>)-one Derivatives: A Novel Class of Anti-Melanogenic Compounds |
| title_full | Design, Synthesis, In Vitro, and In Silico Insights of 5-(Substituted benzylidene)-2-phenylthiazol-4(5<i>H</i>)-one Derivatives: A Novel Class of Anti-Melanogenic Compounds |
| title_fullStr | Design, Synthesis, In Vitro, and In Silico Insights of 5-(Substituted benzylidene)-2-phenylthiazol-4(5<i>H</i>)-one Derivatives: A Novel Class of Anti-Melanogenic Compounds |
| title_full_unstemmed | Design, Synthesis, In Vitro, and In Silico Insights of 5-(Substituted benzylidene)-2-phenylthiazol-4(5<i>H</i>)-one Derivatives: A Novel Class of Anti-Melanogenic Compounds |
| title_short | Design, Synthesis, In Vitro, and In Silico Insights of 5-(Substituted benzylidene)-2-phenylthiazol-4(5<i>H</i>)-one Derivatives: A Novel Class of Anti-Melanogenic Compounds |
| title_sort | design synthesis in vitro and in silico insights of 5 substituted benzylidene 2 phenylthiazol 4 5 i h i one derivatives a novel class of anti melanogenic compounds |
| topic | (<i>Z</i>)-BPT derivatives tyrosinase melanogenesis kojic acid antioxidant in silico |
| url | https://www.mdpi.com/1420-3049/28/8/3293 |
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