title: Evaluation of in vitro and in vivo anti-melanogenic activity of a newly synthesized strong tyrosinase inhibitor (E)-3-(2,4 dihydroxybenzylidene)pyrrolidine-2,5-dione (3-DBP).
abstract: BACKGROUND
  Tyrosinase inhibitors have become increasingly important because of their ability to inhibit the synthesis of the pigment melanin. A search for new agents with strong tyrosinase activity led to the synthesis of the tyrosinase inhibitor (E)-3-(2,4-dihydroxybenzylidene)pyrrolidine-2,5-dione (3-DBP).
  
  
  METHODS
  The inhibitory effect of 3-DBP on tyrosinase activity and melanin production was examined in murine melanoma B16F10 cells. Additional experiments were performed using HRM2 hairless mice to demonstrate the effects of 3-DBP in vivo.
  
  
  RESULTS
  The novel compound, 3-DBP, showed an inhibitory effect against mushroom tyrosinase (IC50=0.53 μM), which indicated that it was more potent than the well-known tyrosinase inhibitor kojic acid (IC50=8.2 μM). When tested in B16F10 melanoma cells treated with α-melanocyte stimulating hormone (α-MSH), 3-DBP also inhibited murine tyrosinase activity, which in turn induced a decrease in melanin production in these cells. The anti-melanogenic effect of 3-DBP was further verified in HRM2 hairless mice. The skin-whitening index (L value) of HRM2 hairless mice treated with 3-DBP before irradiation with UVB was greater than that of UVB-irradiated mice that were not treated with 3-DBP.
  
  
  CONCLUSIONS
  The newly synthesized 3-DBP has a potent inhibitory effect on tyrosinase. In addition to an in vitro investigation of the effects of 3-DBP on tyrosinase, in vivo studies using an HRM2 hairless mouse model demonstrated the anti-melanogenic potency of 3-DBP. Our newly synthesized 3-DBP showed efficient tyrosinase inhibitory effect in vivo and in vitro. Our finding suggests that 3-DBP can be an effective skin-whitening agent.
authors.affiliation: MRCA, Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 609-735, Republic of Korea.
authors.forename: Ki Wung
authors.initials: KW
authors.lastname: Chung
authors.forename: Yun Jung
authors.initials: YJ
authors.lastname: Park
authors.forename: Yeon Ja
authors.initials: YJ
authors.lastname: Choi
authors.forename: Min Hi
authors.initials: MH
authors.lastname: Park
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Ha
authors.forename: Yohei
authors.initials: Y
authors.lastname: Uehara
authors.forename: Jung Hyun
authors.initials: JH
authors.lastname: Yoon
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 / Q000201:enzymology; D000818:Animals; D001597:Benzylidene Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D057886:Bleaching Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008543:Melanins / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008812:Mice, Hairless; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012880:Skin Pigmentation / Q000187:drug effects; D013388:Succinimides / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: C576288:(E)-3-(2,4 dihydroxybenzylidene)pyrrolidine-2,5-dione; D001597:Benzylidene Compounds; D057886:Bleaching Agents; D004791:Enzyme Inhibitors; D008543:Melanins; D013388:Succinimides; D014442:Monophenol Monooxygenase