title: A multifunctional, light-activated prochelator inhibits UVA-induced oxidative stress.
abstract: UVA radiation can damage cells and tissues by direct photodamage of biomolecules as well as by initiating metal-catalyzed oxidative stress. In order to alleviate both concerns simultaneously, we synthesized a multifunctional prochelator PC-HAPI (2-((E)-1-(2-isonicotinoylhydrazono)ethyl)phenyl (trans)-3-(2,4-dihydroxyphenyl)acrylate) that contains a trans-(o-hydroxy)cinnamate ester photocleavable protecting group that is cleaved upon UVA exposure to release a coumarin, umbelliferone, and an aroylhydrazone metal chelator, HAPI (N'-[1-(2-hydroxyphenyl)ethyliden]isonicotinoylhydrazide). While the prochelator PC-HAPI exhibits negligible affinity for iron, it responds rapidly to UVA irradiation and converts to an iron-binding chelator that inhibits iron-catalyzed formation of reactive oxygen species and protects cells from UVA damage.
authors.affiliation: Duke University, Department of Chemistry, 124 Science Dr., Durham, NC 27708, USA.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Franks
authors.affiliation: Duke University, Department of Chemistry, 124 Science Dr., Durham, NC 27708, USA.
authors.forename: Qin
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Duke University, Department of Chemistry, 124 Science Dr., Durham, NC 27708, USA. Electronic address: katherine.franz@duke.edu.
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: Franz
mesh_terms: D000179:Acrylates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002384:Catalysis; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007501:Iron / Q000737:chemistry; D007502:Iron Chelating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D007539:Isonicotinic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D014466:Ultraviolet Rays
chemical_list: C000608312:2-((E)-1-(2-isonicotinoylhydrazono)ethyl)phenyl (trans)-3-(2,4-dihydroxyphenyl)acrylate; D000179:Acrylates; D007502:Iron Chelating Agents; D007539:Isonicotinic Acids; D017382:Reactive Oxygen Species; D007501:Iron
keywords: Antioxidant; Chelator; Oxidative stress; Photocleavage; UVA damage