Discovery of small molecules that inhibit melanogenesis via regulation of tyrosinase expression.
5,6,7,8-Tetrahydro-4H-cyclohepta[d]isoxazole derivatives were synthesized and evaluated as a novel class of inhibitors for α-melanocyte-stimulating hormone (α-MSH) induced melanogenesis in a mouse melanoma B16F10 cell line. Compound 8e (IC(50)=0.67 μM), 8h (IC(50)=1.01 μM) and 9b (IC(50)=0.99 μM) exhibited a potent inhibitory activity approximately 85- to 126-fold greater than kojic acid, a well-known potent inhibitor. A biochemical study indicates that the activity of this series should be displayed via down-regulation of the expression of tyrosinase.
College of Pharmacy, Chung-Ang University, Seoul 156-756, Republic of Korea.
Jiho
J
Song
Hyun-e
HE
Lee
Young Jin
YJ
Kim
Su Yeon
SY
Kim
Dong-Seok
DS
Kim
Kyung Hoon
KH
Min
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D003508:Cycloheptanes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D051379:Mice; D014442:Monophenol Monooxygenase / Q000235:genetics / Q000378:metabolism*; D010879:Piperazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011753:Pyrones / Q000737:chemistry / Q000494:pharmacology; D000521:alpha-MSH / Q000037:antagonists & inhibitors / Q000378:metabolism
D003508:Cycloheptanes; D007555:Isoxazoles; D010879:Piperazines; D011753:Pyrones; D000521:alpha-MSH; C011890:kojic acid; D014442:Monophenol Monooxygenase