Anti-Browning Effect of 2-Mercaptobenzo[<i>d</i>]imidazole Analogs with Antioxidant Activity on Freshly-Cut Apple Slices and Their Highly Potent Tyrosinase Inhibitory Activity
Ten 2-mercaptobenzimidazole (2-MBI) analogs were synthesized as potential tyrosinase inhibitors because mercapto-containing compounds can bind to copper ions at the active site of tyrosinase to inhibit enzyme activity. Nine 2-MBI analogs showed sub-micromolar IC<sub>50</sub> values for m...
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| Format: | Article |
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MDPI AG
2023-09-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/12/10/1814 |
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| author | Jieun Lee Hye Soo Park Hee Jin Jung Yu Jung Park Min Kyung Kang Hye Jin Kim Dahye Yoon Sultan Ullah Dongwan Kang Yujin Park Pusoon Chun Hae Young Chung Hyung Ryong Moon |
| author_facet | Jieun Lee Hye Soo Park Hee Jin Jung Yu Jung Park Min Kyung Kang Hye Jin Kim Dahye Yoon Sultan Ullah Dongwan Kang Yujin Park Pusoon Chun Hae Young Chung Hyung Ryong Moon |
| author_sort | Jieun Lee |
| collection | DOAJ |
| description | Ten 2-mercaptobenzimidazole (2-MBI) analogs were synthesized as potential tyrosinase inhibitors because mercapto-containing compounds can bind to copper ions at the active site of tyrosinase to inhibit enzyme activity. Nine 2-MBI analogs showed sub-micromolar IC<sub>50</sub> values for mushroom tyrosinase monophenolase activity; analog <b>4</b> was 280-fold more potent than kojic acid, and in diphenolase activity, <b>6</b> was 970-fold more potent than kojic acid. The inhibition mode of the 2-MBI analogs was investigated using kinetic studies supported by docking simulations. Benzimidazoles without the 2-mercapto substituent of the 2-MBI analogs lost their tyrosinase inhibitory activity, implying that the 2-mercapto substituent plays an important role in tyrosinase inhibition. The 2-MBI analogs exerted potent antioxidant effects against 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and reactive oxygen species (ROS). The results obtained from apple slices and human embryonic kidney cells (HEK-293) suggest that most 2-MBI analogs are sufficiently safe candidates to delay the browning of apple slices effectively. Thus, these results support the potential use of 2-MBI analogs as anti-browning agents in foods such as mushrooms, vegetables, and fruits. |
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| id | doaj.art-18f948aa94fc4854b9bbd821818257a9 |
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| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T21:29:03Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-18f948aa94fc4854b9bbd821818257a92023-11-19T15:27:34ZengMDPI AGAntioxidants2076-39212023-09-011210181410.3390/antiox12101814Anti-Browning Effect of 2-Mercaptobenzo[<i>d</i>]imidazole Analogs with Antioxidant Activity on Freshly-Cut Apple Slices and Their Highly Potent Tyrosinase Inhibitory ActivityJieun Lee0Hye Soo Park1Hee Jin Jung2Yu Jung Park3Min Kyung Kang4Hye Jin Kim5Dahye Yoon6Sultan Ullah7Dongwan Kang8Yujin Park9Pusoon Chun10Hae Young Chung11Hyung Ryong Moon12Department 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 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 Molecular Medicine, The Herbert Wertheim UF Scripps Institute for Biomedical Innovation & Technology, Jupiter, FL 33458, USADepartment 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 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 KoreaTen 2-mercaptobenzimidazole (2-MBI) analogs were synthesized as potential tyrosinase inhibitors because mercapto-containing compounds can bind to copper ions at the active site of tyrosinase to inhibit enzyme activity. Nine 2-MBI analogs showed sub-micromolar IC<sub>50</sub> values for mushroom tyrosinase monophenolase activity; analog <b>4</b> was 280-fold more potent than kojic acid, and in diphenolase activity, <b>6</b> was 970-fold more potent than kojic acid. The inhibition mode of the 2-MBI analogs was investigated using kinetic studies supported by docking simulations. Benzimidazoles without the 2-mercapto substituent of the 2-MBI analogs lost their tyrosinase inhibitory activity, implying that the 2-mercapto substituent plays an important role in tyrosinase inhibition. The 2-MBI analogs exerted potent antioxidant effects against 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and reactive oxygen species (ROS). The results obtained from apple slices and human embryonic kidney cells (HEK-293) suggest that most 2-MBI analogs are sufficiently safe candidates to delay the browning of apple slices effectively. Thus, these results support the potential use of 2-MBI analogs as anti-browning agents in foods such as mushrooms, vegetables, and fruits.https://www.mdpi.com/2076-3921/12/10/1814browningmelanintyrosinaseantioxidant2-mercaptobenzo[<i>d</i>]imidazoledocking simulation |
| spellingShingle | Jieun Lee Hye Soo Park Hee Jin Jung Yu Jung Park Min Kyung Kang Hye Jin Kim Dahye Yoon Sultan Ullah Dongwan Kang Yujin Park Pusoon Chun Hae Young Chung Hyung Ryong Moon Anti-Browning Effect of 2-Mercaptobenzo[<i>d</i>]imidazole Analogs with Antioxidant Activity on Freshly-Cut Apple Slices and Their Highly Potent Tyrosinase Inhibitory Activity Antioxidants browning melanin tyrosinase antioxidant 2-mercaptobenzo[<i>d</i>]imidazole docking simulation |
| title | Anti-Browning Effect of 2-Mercaptobenzo[<i>d</i>]imidazole Analogs with Antioxidant Activity on Freshly-Cut Apple Slices and Their Highly Potent Tyrosinase Inhibitory Activity |
| title_full | Anti-Browning Effect of 2-Mercaptobenzo[<i>d</i>]imidazole Analogs with Antioxidant Activity on Freshly-Cut Apple Slices and Their Highly Potent Tyrosinase Inhibitory Activity |
| title_fullStr | Anti-Browning Effect of 2-Mercaptobenzo[<i>d</i>]imidazole Analogs with Antioxidant Activity on Freshly-Cut Apple Slices and Their Highly Potent Tyrosinase Inhibitory Activity |
| title_full_unstemmed | Anti-Browning Effect of 2-Mercaptobenzo[<i>d</i>]imidazole Analogs with Antioxidant Activity on Freshly-Cut Apple Slices and Their Highly Potent Tyrosinase Inhibitory Activity |
| title_short | Anti-Browning Effect of 2-Mercaptobenzo[<i>d</i>]imidazole Analogs with Antioxidant Activity on Freshly-Cut Apple Slices and Their Highly Potent Tyrosinase Inhibitory Activity |
| title_sort | anti browning effect of 2 mercaptobenzo i d i imidazole analogs with antioxidant activity on freshly cut apple slices and their highly potent tyrosinase inhibitory activity |
| topic | browning melanin tyrosinase antioxidant 2-mercaptobenzo[<i>d</i>]imidazole docking simulation |
| url | https://www.mdpi.com/2076-3921/12/10/1814 |
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