Identification of a Novel Class of Anti-Melanogenic Compounds, (<i>Z</i>)-5-(Substituted benzylidene)-3-phenyl-2-thioxothiazolidin-4-one Derivatives, and Their Reactive Oxygen Species Scavenging Activities
The rate-determining role of tyrosinase makes it a critical component in the mechanism that is responsible for melanogenesis. Thirteen (<i>Z</i>)-5-(substituted benzylidene)-3-phenyl-2-thioxothiazolidin-4-one ((<i>Z</i>)-BPTT) analogs were designed based on the structural fea...
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MDPI AG
2022-05-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/11/5/948 |
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| author | Yeongmu Jeong Sojeong Hong Hee Jin Jung Sultan Ullah YeJi Hwang Heejeong Choi Jeongin Ko Jieun Lee Pusoon Chun Hae Young Chung Hyung Ryong Moon |
| author_facet | Yeongmu Jeong Sojeong Hong Hee Jin Jung Sultan Ullah YeJi Hwang Heejeong Choi Jeongin Ko Jieun Lee Pusoon Chun Hae Young Chung Hyung Ryong Moon |
| author_sort | Yeongmu Jeong |
| collection | DOAJ |
| description | The rate-determining role of tyrosinase makes it a critical component in the mechanism that is responsible for melanogenesis. Thirteen (<i>Z</i>)-5-(substituted benzylidene)-3-phenyl-2-thioxothiazolidin-4-one ((<i>Z</i>)-BPTT) analogs were designed based on the structural features of two potent tyrosinase inhibitors, viz. (Z)-5-(3-hydroxy-4-methoxybenzylidene)-2-thioxothiazolidin-4-one (5-HMT) and (<i>Z</i>)-2-(2,4-dihydroxybenzylidene)benzo[4,5]imidazo[2,1-<i>b</i>]thiazol-3(2<i>H</i>)-one (compound I). The trisubstituted double bond geometry of the (<i>Z</i>)-BPTT analogs that were generated by Knoevenagel condensation was determined using vicinal <sup>1</sup>H and <sup>13</sup>C coupling constants in <sup>13</sup>C NMR spectra. Four analogs, numbers <b>1</b>–<b>3</b> and <b>6,</b> inhibited mushroom tyrosinase 9 to 29 times more potently than kojic acid did. Kinetic study results indicated that these four analogs inhibited mushroom tyrosinase competitively and this was supported by docking simulation. Also, docking results using human tyrosinase suggested that analogs <b>2</b> and <b>3</b> might be potent human tyrosinase inhibitors. In vitro studies using B16F10 cells (a melanoma cell line) showed that analogs <b>1</b>, <b>2</b>, <b>3</b>, and <b>6</b> inhibited cellular tyrosinase and melanin production more than kojic acid did, without perceptible cytotoxicity. In particular, analog <b>2</b>, which possesses a catechol group, exerted an extremely potent anti-melanogenic effect. In addition, analog <b>2</b> showed strong scavenging activity against DPPH and ABTS radicals. Furthermore, analog <b>2</b> not only reduced ROS levels, which induce melanogenesis, but it also suppressed tyrosinase and MITF (microphthalamia-associated transcription factor) protein levels and the expressions of melanogenesis-related genes. These results suggest that analog <b>2</b> is an efficient tyrosinase inhibitor that alleviates melanogenesis by dual mechanisms of (i) the inhibition of melanogenesis-related proteins and genes and (ii) the direct inhibition of tyrosinase activity. |
| first_indexed | 2024-03-10T03:26:42Z |
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| last_indexed | 2024-03-10T03:26:42Z |
| publishDate | 2022-05-01 |
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| series | Antioxidants |
| spelling | doaj.art-c1b1fb02d43a474dbf02743357cca3442023-11-23T09:52:07ZengMDPI AGAntioxidants2076-39212022-05-0111594810.3390/antiox11050948Identification of a Novel Class of Anti-Melanogenic Compounds, (<i>Z</i>)-5-(Substituted benzylidene)-3-phenyl-2-thioxothiazolidin-4-one Derivatives, and Their Reactive Oxygen Species Scavenging ActivitiesYeongmu Jeong0Sojeong Hong1Hee Jin Jung2Sultan Ullah3YeJi Hwang4Heejeong Choi5Jeongin Ko6Jieun Lee7Pusoon Chun8Hae Young Chung9Hyung Ryong Moon10Laboratory of Medicinal Chemistry, Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaLaboratory of Medicinal Chemistry, Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaDepartment of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaDepartment of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USALaboratory of Medicinal Chemistry, Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaLaboratory of Medicinal Chemistry, Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaLaboratory of Medicinal Chemistry, Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaLaboratory of Medicinal Chemistry, Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaCollege of Pharmacy and Inje Institute of Pharmaceutical Sciences and Research, Inje University, Gimhae 50834, KoreaDepartment of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaLaboratory of Medicinal Chemistry, Department of Manufacturing Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, KoreaThe rate-determining role of tyrosinase makes it a critical component in the mechanism that is responsible for melanogenesis. Thirteen (<i>Z</i>)-5-(substituted benzylidene)-3-phenyl-2-thioxothiazolidin-4-one ((<i>Z</i>)-BPTT) analogs were designed based on the structural features of two potent tyrosinase inhibitors, viz. (Z)-5-(3-hydroxy-4-methoxybenzylidene)-2-thioxothiazolidin-4-one (5-HMT) and (<i>Z</i>)-2-(2,4-dihydroxybenzylidene)benzo[4,5]imidazo[2,1-<i>b</i>]thiazol-3(2<i>H</i>)-one (compound I). The trisubstituted double bond geometry of the (<i>Z</i>)-BPTT analogs that were generated by Knoevenagel condensation was determined using vicinal <sup>1</sup>H and <sup>13</sup>C coupling constants in <sup>13</sup>C NMR spectra. Four analogs, numbers <b>1</b>–<b>3</b> and <b>6,</b> inhibited mushroom tyrosinase 9 to 29 times more potently than kojic acid did. Kinetic study results indicated that these four analogs inhibited mushroom tyrosinase competitively and this was supported by docking simulation. Also, docking results using human tyrosinase suggested that analogs <b>2</b> and <b>3</b> might be potent human tyrosinase inhibitors. In vitro studies using B16F10 cells (a melanoma cell line) showed that analogs <b>1</b>, <b>2</b>, <b>3</b>, and <b>6</b> inhibited cellular tyrosinase and melanin production more than kojic acid did, without perceptible cytotoxicity. In particular, analog <b>2</b>, which possesses a catechol group, exerted an extremely potent anti-melanogenic effect. In addition, analog <b>2</b> showed strong scavenging activity against DPPH and ABTS radicals. Furthermore, analog <b>2</b> not only reduced ROS levels, which induce melanogenesis, but it also suppressed tyrosinase and MITF (microphthalamia-associated transcription factor) protein levels and the expressions of melanogenesis-related genes. These results suggest that analog <b>2</b> is an efficient tyrosinase inhibitor that alleviates melanogenesis by dual mechanisms of (i) the inhibition of melanogenesis-related proteins and genes and (ii) the direct inhibition of tyrosinase activity.https://www.mdpi.com/2076-3921/11/5/948tyrosinaseROSradical scavengingdocking simulationanti-melanogenesisdual mechanism |
| spellingShingle | Yeongmu Jeong Sojeong Hong Hee Jin Jung Sultan Ullah YeJi Hwang Heejeong Choi Jeongin Ko Jieun Lee Pusoon Chun Hae Young Chung Hyung Ryong Moon Identification of a Novel Class of Anti-Melanogenic Compounds, (<i>Z</i>)-5-(Substituted benzylidene)-3-phenyl-2-thioxothiazolidin-4-one Derivatives, and Their Reactive Oxygen Species Scavenging Activities Antioxidants tyrosinase ROS radical scavenging docking simulation anti-melanogenesis dual mechanism |
| title | Identification of a Novel Class of Anti-Melanogenic Compounds, (<i>Z</i>)-5-(Substituted benzylidene)-3-phenyl-2-thioxothiazolidin-4-one Derivatives, and Their Reactive Oxygen Species Scavenging Activities |
| title_full | Identification of a Novel Class of Anti-Melanogenic Compounds, (<i>Z</i>)-5-(Substituted benzylidene)-3-phenyl-2-thioxothiazolidin-4-one Derivatives, and Their Reactive Oxygen Species Scavenging Activities |
| title_fullStr | Identification of a Novel Class of Anti-Melanogenic Compounds, (<i>Z</i>)-5-(Substituted benzylidene)-3-phenyl-2-thioxothiazolidin-4-one Derivatives, and Their Reactive Oxygen Species Scavenging Activities |
| title_full_unstemmed | Identification of a Novel Class of Anti-Melanogenic Compounds, (<i>Z</i>)-5-(Substituted benzylidene)-3-phenyl-2-thioxothiazolidin-4-one Derivatives, and Their Reactive Oxygen Species Scavenging Activities |
| title_short | Identification of a Novel Class of Anti-Melanogenic Compounds, (<i>Z</i>)-5-(Substituted benzylidene)-3-phenyl-2-thioxothiazolidin-4-one Derivatives, and Their Reactive Oxygen Species Scavenging Activities |
| title_sort | identification of a novel class of anti melanogenic compounds i z i 5 substituted benzylidene 3 phenyl 2 thioxothiazolidin 4 one derivatives and their reactive oxygen species scavenging activities |
| topic | tyrosinase ROS radical scavenging docking simulation anti-melanogenesis dual mechanism |
| url | https://www.mdpi.com/2076-3921/11/5/948 |
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