Discovery, Synthetic Methodology, and Biological Evaluation for Antiphotoaging Activity of Bicyclic[1,2,3]triazoles: In Vitro and in Vivo Studies

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• 作者：Hsin-Yu Hsieh ; Wen-Chun Lee ; Gopal Chandru Senadi ; Wan-Ping Hu ; Jium-Jia Liang ; Tong-Rong Tsai ; Yu-Wei Chou ; Kung-Kai Kuo ; Chung-Yu Chen ; Jeh-Jeng Wang
• 刊名：Journal of Medicinal Chemistry
• 出版年：2013
• 出版时间：July 11, 2013
• 年：2013
• 卷：56
• 期：13
• 页码：5422-5435
• 全文大小：646K
• 年卷期：v.56,no.13(July 11, 2013)
• ISSN：1520-4804

文摘

Novel bicyclic[1,2,3]triazoles (4, 7, 11, 15) have been synthesized using a one-pot metal free strategy with high structural diversity as photoprotective agents, and their effect on UVA-induced senescence in human dermal fibroblast cells (FB) and the associated mechanism are delineated. 11d plus UVA can induce a decrease in reactive oxygen species (ROS) production and senescence-associated 尾-galactosidase (SA-尾-gal) activity but an increase in adenosine triphosphate (ATP) synthesis and mitochondrial membrane potential (螖唯_mt). The mRNA levels of six senescence-associated genes, matrix metalloproteinase-1 (MMP-1), was decreased, while elastin, procollagen I type I, fibronectin, COL1伪1, and tissue inhibitor of metalloproteinase-1 (TIMP-1) were increased. 11d plus UVA also decreased MMP-1 and increased TIMP-1 protein levels. Additionally, the thickness of the murine dorsal skin and epidermis, by UVA, was decreased by topical 11d treatment. Our results indicate that bicyclic[1,2,3]triazoles protect UVA-induced senescence-like characteristics in FB cells, which may provide potential prevention against photoaging.