title: Discovery, synthetic methodology, and biological evaluation for antiphotoaging activity of bicyclic[1,2,3]triazoles: in vitro and in vivo studies.
abstract: 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 β-galactosidase (SA-β-gal) activity but an increase in adenosine triphosphate (ATP) synthesis and 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. 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.
authors.affiliation: Department of Medicinal and Applied Chemistry,‡Department of Biotechnology, §School of Pharmacy, and ⊥Department of Surgery, School of Medicine, Kaohsiung Medical University , Kaohsiung, Taiwan.
authors.forename: Hsin-Yu
authors.initials: HY
authors.lastname: Hsieh
authors.forename: Wen-Chun
authors.initials: WC
authors.lastname: Lee
authors.forename: Gopal Chandru
authors.initials: GC
authors.lastname: Senadi
authors.forename: Wan-Ping
authors.initials: WP
authors.lastname: Hu
authors.forename: Jium-Jia
authors.initials: JJ
authors.lastname: Liang
authors.forename: Tong-Rong
authors.initials: TR
authors.lastname: Tsai
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Chou
authors.forename: Kung-Kai
authors.initials: KK
authors.lastname: Kuo
authors.forename: Chung-Yu
authors.initials: CY
authors.lastname: Chen
authors.forename: Jeh-Jeng
authors.initials: JJ
authors.lastname: Wang
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D015195:Drug Design; D004549:Elastin / Q000235:genetics / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D015151:Immunoblotting; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D008956:Models, Chemical; D015394:Molecular Structure; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D015595:Skin Aging / Q000187:drug effects* / Q000528:radiation effects; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014466:Ultraviolet Rays
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D005353:Fibronectins; D017382:Reactive Oxygen Species; D019715:Tissue Inhibitor of Metalloproteinase-1; D014230:Triazoles; D004549:Elastin; D020781:Matrix Metalloproteinase 1