title: Expedited access to vinaxanthone and chemically edited derivatives possessing neuronal regenerative effects through ynone coupling reactions.
abstract: The natural product vinaxanthone has demonstrated a remarkable capability to promote nerve growth following injury or transplantation. In rats following total transection of the spinal cord delivery of vinaxanthone enhanced axonal regeneration, remyelination and angiogenesis at the site of injury all leading to an improved reinstatement of motor function. Through the development of a new ynone coupling reaction, chemically edited derivatives of vinaxanthone have been prepared and studied for improved activity. The coupling reaction allows rapid access to new derivatives, wherein n ynone precursors provide n(2) vinaxanthone analogues. These compounds have been tested for their ability to promote neuronal regrowth using laser axotomy, severing axonal connections in Caenorhabditis elegans. This precise microsurgery using C. elegans allows a new in vivo approach for medicinal chemistry based optimization of neuronal growth promoting compounds.
authors.affiliation: †Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, United States.|‡Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92039, United States.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Chin
authors.affiliation: †Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, United States.|‡Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92039, United States.
authors.forename: Katherine
authors.initials: K
authors.lastname: Zlotkowski
authors.affiliation: †Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, United States.
authors.forename: Michelle
authors.initials: M
authors.lastname: Han
authors.affiliation: †Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, United States.
authors.forename: Saagar
authors.initials: S
authors.lastname: Patel
authors.affiliation: †Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, United States.|‡Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92039, United States.
authors.forename: Anders M
authors.initials: AM
authors.lastname: Eliasen
authors.affiliation: †Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, United States.
authors.forename: Abram
authors.initials: A
authors.lastname: Axelrod
authors.affiliation: †Department of Chemistry, The University of Texas at Austin, Austin, Texas 78712, United States.|‡Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California 92039, United States.
authors.forename: Dionicio
authors.initials: D
authors.lastname: Siegel
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D017173:Caenorhabditis elegans; D002867:Chromones / Q000138:chemical synthesis / Q000737:chemistry; D019281:Dimerization; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007834:Lasers; D008866:Microsurgery; D015394:Molecular Structure; D009416:Nerve Regeneration / Q000187:drug effects; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D014867:Water / Q000737:chemistry; D044004:Xanthones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002867:Chromones; D018696:Neuroprotective Agents; D044004:Xanthones; C477901:xanthofulvin; D014867:Water; C086647:vinaxanthone
keywords: C. elegans; Vinaxanthone; analogue synthesis; laser axotomy; regeneration; spinal cord injury