Synthesis and Protective Effects of Bis{4-[N,N-di-(carboxymethyl)amino]phenoxy}alkane Derivatives on UVA-Induced Production of MMP-1 in Human Skin Fibroblasts

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  • Hsu Ling-Yih
    Department of Biological Science and Technology, China University of Science and Technology
  • Nien Chih-Ying
    School of Pharmacy, National Defense Medical Center
  • Huang Wei-Ming
    Department of Biochemistry, National Defense Medical Center
  • Hsu Shou-Che
    Department of Biochemistry, National Defense Medical Center
  • Chang Tsu-Chung
    Department of Biotechnology, Asia University Graduate Institute of Basic Medical Science, China Medical University Department of Biochemistry, National Defense Medical Center

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  • Synthesis and Protective Effects of Bis{4-[<i>N</i>,<i>N</i>-di-(carboxymethyl)amino]phenoxy}alkane Derivatives on UVA-Induced Production of MMP-1 in Human Skin Fibroblasts

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UV-induced matrix metalloproteinase (MMP) production is considered a cause of skin aging. In this study, a number of novel bis{4-[N,N-di-(carboxymethyl)amino]phenoxy}alkane derivatives were synthesized and evaluated as UVA-protective agents. These compounds significantly protected human dermal fibroblast (HDF) cells from UVA-induced cytotoxicity and inhibited MMP-1 activation and expression with potency comparable to desferoxamine (DFO). Promoter activity assay indicated that they inhibited MMP-1 expression at the transcriptional level. Further studies revealed that the mechanism of these compounds may include blockage of the UVA-induced activation of the p38/mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK) pathways. Together, these results suggest that further development of these compounds may be of interest.

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