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

Abstract

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.