title: Alkaloids from Alangium javanicum and Alangium grisolleoides that mediate Cu2+-dependent DNA strand scission.
abstract: Crude CH2Cl2-MeOH extracts prepared from Alangium javanicum and A. grisolleoides were found to induce DNA strand breakage in the presence of Cu2+ and were subjected to bioassay-guided fractionation to permit identification of the active principle(s). Javaniside (1), a novel alkaloid possessing an unusual monoterpenoid oxindole skeleton, was identified as an active principle contributing to the DNA cleavage activity observed for the crude extract of A. javanicum. Alangiside (2), a tetrahydroisoquinoline monoterpene glucoside widely distributed in the genus Alangium, was also isolated from A. grisolleoides as a new type of Cu2+-dependent DNA cleavage agent. The relative configuration of the asymmetric centers in javaniside was established by analysis of 1H-1H coupling constants and NOESY correlations. Semisynthesis of javaniside from secologanin (3) established the absolute stereochemistry of javaniside.
authors.affiliation: Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901, USA.
authors.forename: Van Cuong
authors.initials: VC
authors.lastname: Pham
authors.forename: Ji
authors.initials: J
authors.lastname: Ma
authors.forename: Shannon J
authors.initials: SJ
authors.lastname: Thomas
authors.forename: Zhidong
authors.initials: Z
authors.lastname: Xu
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Hecht
mesh_terms: D032604:Alangiaceae / Q000737:chemistry*; D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D026121:Indole Alkaloids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015394:Molecular Structure; D039821:Monoterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D010946:Plants, Medicinal / Q000737:chemistry*; D044005:Tetrahydroisoquinolines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology
chemical_list: D000470:Alkaloids; D005960:Glucosides; D026121:Indole Alkaloids; D039821:Monoterpenes; D044005:Tetrahydroisoquinolines; C504105:alangiside; C504104:javaniside; D003300:Copper; D004247:DNA