title: Design, synthesis, and evaluation of (E)-N-substituted benzylidene-aniline derivatives as tyrosinase inhibitors.
abstract: We attempted to design and synthesize (E)-N-substituted benzylidene-hydroxy or methoxy-aniline derivatives and to evaluate their inhibitory effect on tyrosinase activity and anti-melanogenesis activity in murine B16F10 melanoma cells. Derivatives with a 4-methoxy- or 4-hydroxy-anilino group exerted more potent inhibition against mushroom tyrosinase than those with a 2-hydroxyanilino group. (E)-4-((4-Hydroxyphenylimino)methyl)benzene-1,2-diol exhibited the most potent and non-competitive inhibition on mushroom tyrosinase showing an IC(50) of 17.22 ± 0.38 μM and being more effective than kojic acid (51.11 ± 1.42 μM). This compound decreased melanin production stimulated by the alpha-melanocyte-stimulating hormone and inhibited murine tyrosinase activity in a dose-dependent manner. Therefore, we propose (E)-4-((4-hydroxyphenylimino)methyl)benzene-1,2-diol as a new candidate of potent tyrosinase inhibitors that could be used as therapeutic agent with safe skin-whitening efficiency.
authors.affiliation: Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Kumjeong-Gu, Busan 609-735, 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: Yun Jung
authors.initials: YJ
authors.lastname: Park
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Park
authors.forename: Yu Min
authors.initials: YM
authors.lastname: Song
authors.forename: Tae Kwun
authors.initials: TK
authors.lastname: Ha
authors.forename: Pusoon
authors.initials: P
authors.lastname: Chun
authors.forename: Hyung Ryong
authors.initials: HR
authors.lastname: Moon
authors.forename: Hae Young
authors.initials: HY
authors.lastname: Chung
mesh_terms: D000363:Agaricales / Q000737:chemistry; D000814:Aniline Compounds / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001597:Benzylidene Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D002396:Catechols / Q000138:chemical synthesis* / Q000494:pharmacology; 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* / Q000096:biosynthesis; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000201:enzymology; D051379:Mice; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011753:Pyrones / Q000494:pharmacology; D012545:Schiff Bases / Q000138:chemical synthesis* / Q000494:pharmacology; D012878:Skin Neoplasms / Q000188:drug therapy / Q000201:enzymology; D014407:Tumor Cells, Cultured; D000521:alpha-MSH / Q000494:pharmacology
chemical_list: C580935:4-((4-hydroxyphenylimino)methyl)benzene-1,2-diol; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D002396:Catechols; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D008543:Melanins; D011753:Pyrones; D012545:Schiff Bases; D000521:alpha-MSH; C011890:kojic acid; D014442:Monophenol Monooxygenase; C023650:aniline