Synthesis of tyrosinase inhibitory kojic acid derivative.
Kojic acid derivative 2 was synthesized by joining two pyrone rings through an ethylene linkage by Horner-Emmons reaction of phosphonate 6 with aldehyde 7. The intermediates 6 and 7 were derived from kojic acid. The tyrosinase inhibitory activity of 2 was about 8 times more potent (IC(50) = 3.63 microM) than that of kojic acid (IC(50) = 30.61 microM). Compound 2 also exhibited potent melanin synthesis inhibitory activity (19.53% inhibition at 5 mug) indicating that the connection of two pyrone rings of kojic acid through a suitable linker can be an useful strategy for identification of potent tyrosinase inhibitors.
Lee
Yong Sup
YS
Division of Life Sciences, Korea Institute of Science and Technology, Seoul, Korea. kyslee@khu.ac.kr
Park
Jang Hyun
JH
Kim
Min Hwan
MH
Seo
Seon Hee
SH
Kim
Hyoung Ja
HJ
D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008543:Melanins / Q000096:biosynthesis / Q000502:physiology; D008546:Melanoma, Experimental / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D014442:Monophenol Monooxygenase / Q000009:adverse effects*; D011753:Pyrones / Q000138:chemical synthesis* / Q000494:pharmacology; D012880:Skin Pigmentation / Q000187:drug effects; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D004791:Enzyme Inhibitors; D008543:Melanins; D011753:Pyrones; D014442:Monophenol Monooxygenase