Alkaloids from Alangium javanicum and Alangium grisolleoides that mediate Cu2+-dependent DNA strand scission.
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.
Pham
Van Cuong
VC
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901, USA.
Ma
Ji
J
Thomas
Shannon J
SJ
Xu
Zhidong
Z
Hecht
Sidney M
SM
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
D000470:Alkaloids; D005960:Glucosides; D026121:Indole Alkaloids; D039821:Monoterpenes; D044005:Tetrahydroisoquinolines; C504105:alangiside; C504104:javaniside; D003300:Copper; D004247:DNA