Use of COMPARE analysis to discover functional analogues of bleomycin.
Bleomycin was used as the reference compound in a COMPARE analysis to identify extracts in the National Cancer Institute's Natural Products Repository exhibiting cytotoxicity profiles similar to this antitumor agent. One of the extracts so identified was a CH(2)Cl(2)-methanol extract prepared from Gymnosporia trigyna, which effected relaxation of supercoiled pSP64 DNA in the presence of Cu(2+). Bioassay-guided fractionation using DNA strand-scission activity as an end point resulted in the isolation of four active principles. These were identified as syringaldehyde (1), (-)-syringaresinol (2), (+)-catechin (3), and (+)-epicatechin (4). Compounds 1 and 2 represent a new type of DNA strand-scission agent.
Deng
J Z
JZ
Departments of Chemistry and Biology, University of Virginia, Charlottesville, Virginia 22901, USA.
Newman
D J
DJ
Hecht
S M
SM
D000465:Algorithms; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001761:Bleomycin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004247:DNA / Q000737:chemistry / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor / Q000379:methods*
D000903:Antibiotics, Antineoplastic; D001761:Bleomycin; D004247:DNA