Characterization of a small molecule inhibitor of melanogenesis that inhibits tyrosinase activity and scavenges nitric oxide (NO)

被引：38

作者：

Chung, Ki Wung ^{[1
]}

Jeong, Hyoung Oh ^{[1
]}

Jang, Eun Ji ^{[1
]}

Choi, Yeon Ja ^{[1
]}

Kim, Dae Hyun ^{[1
]}

Kim, So Ra ^{[1
]}

Lee, Kyung Jin ^{[1
,2
]}

Lee, Hye Jin ^{[1
,2
]}

Chun, Pusoon ^{[3
]}

Byun, Youngjoo ^{[4
]}

Moon, Hyung Ryong ^{[1
,2
]}

Chung, Hae Young ^{[1
]}

机构：

[1] Pusan Natl Univ, Dept Pharm, Mol Inflammat Res Ctr Aging Intervent MRCA, Pusan 609735, South Korea

[2] Pusan Natl Univ, Coll Pharm, Med Chem Lab, Pusan 609735, South Korea

[3] Inje Univ, Coll Pharm, Gimhae 621749, Gyeongnam, South Korea

[4] Korea Univ, Coll Pharm, Chungnam 339700, South Korea

来源：

BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS | 2013年 / 1830卷 / 10期

基金：

新加坡国家研究基金会;

关键词：

Melanogenesis; Tyrosinase inhibitor; Nitric oxide (NO); HRM2 hairless mouse; HUMAN MELANOCYTES; PIGMENTATION; SKIN; AGENTS;

D O I：

10.1016/j.bbagen.2013.06.002

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Background: Excessive melanin production and accumulation are characteristics of a large number of skin diseases, including melasma, and post-inflammatory hyperpigmentation. During our on-going search for new agents with an inhibitory effect on tyrosinase, we synthesized a new type of tyrosinase inhibitor, 4-(thiazolidin-2-yl)benzene-1,2-diol (MHY-794), which directly inhibits mushroom tyrosinase. Methods: The inhibitory effect of MHY-794 on tyrosinase activity and nitric oxide (NO) scavenging activity was evaluated in cell free system. Additional experiments were performed using B16F10 melanoma cells to demonstrate the effects of MHY-794 in vitro. HRM2 hairless mice were used to evaluate anti-melanogenic effects of MHY-794 in vivo. Results: MHY-794 effectively inhibited mushroom tyrosinase activity in cell free system. In silica docking simulation also supported the inhibitory effects of MHY-794 on mushroom tyrosinase. MHY-794 also proved to be effective at scavenging nitric oxide (NO), which serves as an important modulator in the melanogenesis signaling pathway. In addition, MHY-794 effectively inhibited SNP (NO donor)-induced melanogenesis by directly inhibiting tyrosinase and diminishing NO-mediated melanogenesis signaling in B16 melanoma cells. The anti-melanogenic effects of MHY-794 were further confirmed in HRM2 hairless mice. Ultraviolet light (UV) significantly up-regulated NO-mediated melanogenesis signaling in HRM2 hairless mice, but MHY-794 effectively inhibited both melanogenesis and diminished UV-induced NO-signaling. Conclusions: Our results indicate that MHY-794 is highly effective at inhibiting NO-mediated melanogenesis in vitro and in vivo by direct NO scavenging and directly inhibiting tyrosinase activity, and suggest that MHY-794 be considered a new developmental candidate for the treatment of hyper-pigmentation disorders. General significance: MHY-794, which showed great efficacy on NO-mediated melanogenesis by direct NO scavenging as well as direct inhibition of tyrosinase catalytic activity, might be utilized for the development of a new candidate for treatment of the hyper-pigmentation disorders. (c) 2013 Elsevier B.V. All rights reserved.

引用

页码：4752 / 4761

页数：10

共 27 条

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