title: Umbelactonyl cinnamate derivatives from Crypteronia paniculata that mediate DNA strand scission.
abstract: As part of an initiative to discover functional natural product analogues of bleomycin guided by the use of the COMPARE algorithm, a CH(2)Cl(2)-MeOH extract prepared from Crypteronia paniculata was found to exhibit relaxation of supercoiled pSP64 DNA in the presence of Cu(2+). Bioassay-guided fractionation employing a DNA strand scission assay resulted in the isolation of three novel DNA cleavage agents. Their structures were elucidated as umbelactonyl cinnamate derivatives 1-3 through their NMR and MS spectral data analyses. This is the first example of the isolation and structural characterization of naturally occurring umbelactonyl cinnamate derivatives. Compound 1 exhibited strong Cu(2+)-dependent relaxation of supercoiled pSP64 DNA, while compounds 2 and 3 had only weak DNA cleavage activity.
authors.affiliation: Departments of Chemistry and Biology, University of Virginia, Charlottesville, Virginia 22901, USA.
authors.forename: Jing-Zhen
authors.initials: JZ
authors.lastname: Deng
authors.forename: David J
authors.initials: DJ
authors.lastname: Newman
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Hecht
mesh_terms: D000465:Algorithms; D002109:Caffeic Acids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D003300:Copper / Q000737:chemistry; D003373:Coumaric Acids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry*; D005663:Furans / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D010679:Philippines; D010946:Plants, Medicinal / Q000737:chemistry*
chemical_list: D002109:Caffeic Acids; D003373:Coumaric Acids; D005663:Furans; C499726:umbelactonyl caffeate; C499727:umbelactonyl hydroxycinnamate; D003300:Copper; D004247:DNA