title: Design, synthesis and biological evaluation of 2-(substituted phenyl)thiazolidine-4-carboxylic acid derivatives as novel tyrosinase inhibitors.
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.
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention, College of Pharmacy, Pusan National University, Kumjeong-Gu, Busan 609-735, Republic of Korea.
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Ha
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Park
authors.forename: Ji Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Daeui
authors.initials: D
authors.lastname: Park
authors.forename: Yeon Ja
authors.initials: YJ
authors.lastname: Choi
authors.forename: Eun Kyeong
authors.initials: EK
authors.lastname: Lee
authors.forename: Ji Min
authors.initials: JM
authors.lastname: Kim
authors.forename: Jin-Ah
authors.initials: JA
authors.lastname: Kim
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Park
authors.forename: Hye Jin
authors.initials: HJ
authors.lastname: Lee
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000363:Agaricales / Q000201:enzymology; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D007700:Kinetics; D007980:Levodopa / Q000737:chemistry; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D008958:Models, Molecular; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010670:Phenylthiourea / Q000737:chemistry; D017434:Protein Structure, Tertiary; D053778:Thiazolidines / Q000138:chemical synthesis* / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014443:Tyrosine / Q000737:chemistry; D000521:alpha-MSH / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D008543:Melanins; D053778:Thiazolidines; D014443:Tyrosine; D007980:Levodopa; D000521:alpha-MSH; D010670:Phenylthiourea; C003438:thiazolidine-4-carboxylic acid; D014442:Monophenol Monooxygenase