Design, synthesis and biological evaluation of 2-(substituted phenyl)thiazolidine-4-carboxylic acid derivatives as novel tyrosinase inhibitors |
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Authors: | Ha Young Mi Park Yun Jung Lee Ji Yeon Park Daeui Choi Yeon Ja Lee Eun Kyeong Kim Ji Min Kim Jin-Ah Park Ji Young Lee Hye Jin Moon Hyung Ryong Chung Hae Young |
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Institution: | Molecular Inflammation Research Center for Aging Intervention, College of Pharmacy, Pusan National University, Kumjeong-Gu, Busan 609-735, Republic of Korea. |
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Abstract: | Herein we describe the design, synthesis and biological activities of 2-(substituted phenyl)thiazolidine-4-carboxylic acid derivatives as novel tyrosinase inhibitors. The target compounds 2a–2j were designed and synthesized from the structural characteristics of N-phenylthiourea, tyrosinase inhibitor and tyrosine, and l-DOPA, the natural substrates of tyrosinase. Among them, (2R/S,4R)-2-(2,4-dimethoxyphenyl)thiazolidine-4-carboxylic acid (2g) caused the greatest inhibition 66.47% at 20 μM of l-DOPA oxidase activity of mushroom tyrosinase. Kinetic analysis of tyrosinase inhibition revealed that 2g is a competitive inhibitor. We predicted the tertiary structure of tyrosinase, and simulated the docking of mushroom tyrosinase with 2g. These results suggest that the binding affinity of 2g with tyrosinase is high. Also, 2g effectively inhibited tyrosinase activity and reduced melanin levels in B16 cells treated with α-MSH. These data strongly suggest that 2g can suppress the production of melanin via the inhibition of tyrosinase activity. |
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Keywords: | Melanin biosynthesis Tyrosinase inhibitor Hyperpigmentation Docking analysis 2-(Substituted phenyl)thiazolidine-4-carboxylic acid derivatives |
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