Lee Jieun, Park Hye Soo, Jung Hee Jin, Park Yu Jung, Kang Min Kyung, Kim Hye Jin, Yoon Dahye, Ullah Sultan, Kang Dongwan, Park Yujin, Chun Pusoon, Chung Hae Young, Moon Hyung Ryong
Department of Manufacturing Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea.
Department of Pharmacy, College of Pharmacy and Research Institute for Drug Development, Pusan National University, Busan 46241, Republic of Korea.
Antioxidants (Basel). 2023 Sep 29;12(10):1814. doi: 10.3390/antiox12101814.
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 values for mushroom tyrosinase monophenolase activity; analog was 280-fold more potent than kojic acid, and in diphenolase activity, 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.
合成了十种2-巯基苯并咪唑（2-MBI）类似物作为潜在的酪氨酸酶抑制剂，因为含巯基的化合物可以与酪氨酸酶活性位点的铜离子结合以抑制酶活性。九种2-MBI类似物对蘑菇酪氨酸酶单酚酶活性显示出亚微摩尔IC值；类似物 比曲酸的效力高280倍，在二酚酶活性方面， 比曲酸的效力高970倍。使用对接模拟支持的动力学研究对2-MBI类似物的抑制模式进行了研究。没有2-MBI类似物的2-巯基取代基的苯并咪唑失去了酪氨酸酶抑制活性，这意味着2-巯基取代基在酪氨酸酶抑制中起重要作用。2-MBI类似物对2,2'-偶氮双（3-乙基苯并噻唑啉-6-磺酸）（ABTS）、2,2-二苯基-1-苦基肼（DPPH）和活性氧（ROS）具有强大的抗氧化作用。从苹果切片和人胚肾细胞（HEK-293）获得的结果表明，大多数2-MBI类似物是足够安全的候选物，能够有效地延迟苹果切片的褐变。因此，这些结果支持2-MBI类似物作为蘑菇、蔬菜和水果等食品中的抗褐变剂的潜在用途。
