title: Small molecular inhibitors of miR-1 identified from photocycloadducts of acetylenes with 2-methoxy-1,4-naphthalenequinone.
abstract: Small molecules which can modulate endogenous microRNAs are important chemical tools to study microRNA regulational network. In this Letter we screened the [2+2] photocycloadducts of 2-methoxy-1,4-naphthalenequinone with a series of aryl acetylenes on their activity to modulate endogenous microRNAs. A potent inhibitor of the muscle-specific miR-1 which is closely related with cardiac development and disease was identified. The small molecular inhibitor was the cyclobutene type product derived from the photocycloaddition of 2-methoxy-1,4-naphthalenequinone with tert-butyl (5-(phenylethynyl)quinolin-8-yl) carbonate. Analogues of the small molecular inhibitor were then prepared using similar photocycloaddition reactions for evaluation on inhibition activity on miR-1 to provide structure-activity relationship of the miR-1 inhibitor.
authors.affiliation: School of Life Science, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Su-Bee
authors.initials: SB
authors.lastname: Tan
authors.forename: Chengmei
authors.initials: C
authors.lastname: Huang
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Chen
authors.forename: Yihan
authors.initials: Y
authors.lastname: Wu
authors.forename: Mi
authors.initials: M
authors.lastname: Zhou
authors.forename: Chenyu
authors.initials: C
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000480:Alkynes / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D045744:Cell Line, Tumor; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D009281:Naphthalenes / Q000737:chemistry / Q000494:pharmacology*; D055668:Photochemical Processes; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000480:Alkynes; D035683:MicroRNAs; D009281:Naphthalenes; D054852:Small Molecule Libraries
keywords: 2-Methoxy-1,4-naphthalenequinone; Acetylene; Cyclobutene; Inhibitor of miR-1; Photocycloaddition