Umbelactonyl cinnamate derivatives from Crypteronia paniculata that mediate DNA strand scission

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.