Discovery,Synthetic Methodology, and Biological Evaluationfor Antiphotoaging Activity of Bicyclic[1,2,3]triazoles: In Vitroand in Vivo Studies.

Novelbicyclic[1,2,3]triazoles (4, 7, 11, 15) have been synthesized using a one-potmetal free strategy with high structural diversity as photoprotectiveagents, and their effect on UVA-induced senescence in human dermalfibroblast cells (FB) and the associated mechanism are delineated. 11dplus UVA can induce a decrease in reactive oxygen species(ROS) production and senescence-associated β-galactosidase (SA-β-gal)activity but an increase in adenosine triphosphate (ATP) synthesisand mitochondrial membrane potential (ΔΨmt).The mRNA levels of six senescence-associated genes, matrix metalloproteinase-1(MMP-1), was decreased, while elastin, procollagen I type I, fibronectin,COL1α1, and tissue inhibitor of metalloproteinase-1 (TIMP-1)were increased. 11dplus UVA also decreased MMP-1 andincreased TIMP-1 protein levels. Additionally, the thickness of themurine dorsal skin and epidermis, by UVA, was decreased by topical 11dtreatment. Our results indicate that bicyclic[1,2,3]triazolesprotect UVA-induced senescence-like characteristics in FB cells, whichmay provide potential prevention against photoaging. [ABSTRACT FROM AUTHOR]