title: A novel synthesized tyrosinase inhibitor: (E)-2-((2,4-dihydroxyphenyl)diazenyl)phenyl 4-methylbenzenesulfonate as an azo-resveratrol analog.
abstract: We synthesized a novel series of (E)-2-((substituted phenyl)diazenyl)phenyl 4-methylbenzenesulfonate derivatives (2 and 3) and (E)-2-((substituted phenyl)diazenyl)phenol derivatives (4 and 5), and conducted an evaluation in order to determine their inhibitory effects on mushroom tyrosinase, with the aim of discovering a tyrosinase inhibitor. Most of the compounds (3-5) exhibited higher inhibitory effects than kojic acid (IC(50) = 49.08 µM), a representative tyrosinase inhibitor. A novel synthesized compound, (E)-2-((2,4-dihydroxyphenyl)diazenyl)phenyl 4-methylbenzenesulfonate (3), showed the best results with an IC(50) of 17.85 µM, and showed competitive inhibition on Lineweaver-Burk plots, as further confirmed by the docking results. In addition, active compounds 3-5 were not cytotoxic to cultured B16F10 cells at the concentrations tested, and inhibited both tyrosinase and melanin synthesis. Therefore the active compounds (3-5) might be considered excellent candidates for use in the development of therapeutic agents for diseases associated with hyperpigmentation.
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention, College of Pharmacy, Pusan National University, Busan, Republic of Korea.
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Bae
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Ha
authors.forename: Jin-Ah
authors.initials: JA
authors.lastname: Kim
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Park
authors.forename: Tae Kwun
authors.initials: TK
authors.lastname: Ha
authors.forename: Daeui
authors.initials: D
authors.lastname: Park
authors.forename: Pusoon
authors.initials: P
authors.lastname: Chun
authors.forename: Nam Hee
authors.initials: NH
authors.lastname: Park
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000818:Animals; D001391:Azo Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D001557:Benzenesulfonates / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D057075:Enzyme Assays; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007700:Kinetics; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008546:Melanoma, Experimental / Q000378:metabolism; D051379:Mice; D062105:Molecular Docking Simulation; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010859:Pigmentation Disorders / Q000188:drug therapy; D011753:Pyrones / Q000494:pharmacology; D000077185:Resveratrol; D013267:Stilbenes / Q000737:chemistry*
chemical_list: C582063:2-((2,4-dihydroxyphenyl)diazenyl)phenyl 4-methylbenzenesulfonate; D001391:Azo Compounds; D001557:Benzenesulfonates; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D008543:Melanins; D011753:Pyrones; D013267:Stilbenes; C011890:kojic acid; D014442:Monophenol Monooxygenase; D000077185:Resveratrol