Development of 5-[(3-aminopropyl)phosphinooxy]-2-(hydroxymethyl)-4H-pyran-4-one as a novel whitening agent.
A stable derivative of kojic acid, 5-[(3-aminopropyl)phosphinooxy]-2-(hydroxymethyl)-4H-pyran-4-one (Kojyl-APPA), was synthesized in good yield. The effects of Kojyl-APPA on tyrosinase activity and melanin synthesis were investigated. Kojyl-APPA showed tyrosinase inhibition effect (30%) in situ, but not in vitro. Kojyl-APPA inhibited tyrosinase activity significantly at 24 h after treatment in normal human melanocytes. It means that Kojyl-APPA is not a direct inhibitor of tyrosinase itself, but it is converted to a potential inhibitor kojic acid enzymatically in cells. In addition, Kojyl-APPA decreased melanin content to 75% of control in melanoma cells and decreased neomelanin synthesis to 43% of control in normal human melanocytes. Its permeation through skin increased by about 8 times as compared with kojic acid.
Kim
Duck Hee
DH
R&D Center, Amore-Pacific Corporation, Borari, Kiheung-up, Yongin-si, Kyounggi-do, Korea.
Hwang
Jae-Sung
JS
Baek
Heung Soo
HS
Kim
Kil-Joong
KJ
Lee
Byeong Gon
BG
Chang
Ihseop
I
Kang
Hak Hee
HH
Lee
Ok Sub
OS
D000818:Animals; D003879:Dermatologic Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008543:Melanins / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism; D051379:Mice; D011753:Pyrones / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000378:metabolism; D012880:Skin Pigmentation / Q000187:drug effects / Q000502:physiology; D013678:Technology, Pharmaceutical / Q000379:methods*; D014407:Tumor Cells, Cultured
D003879:Dermatologic Agents; D008543:Melanins; D011753:Pyrones; C011890:kojic acid