DNA damaging activity of ellagic acid derivatives.
A strain of yeast rendered repair deficient by the conditional expression of the RAD52 locus was used to search for natural products capable of damaging DNA. Four ellagic acid derivatives, namely 3,3'-dimethyl-4'-O-beta-D-glucopyranosyl ellagic acid (1), 3,3',4-trimethyl-4'-O-beta-D-glucopyranosyl ellagic acid (2), 3'-methyl-3,4-O,O-methylidene ellagic acid (3) and 3'-methyl-3,4-O,O-methylidene-4'-O-beta-D-glucopyranosyl ellagic acid (4), were identified by this assay as DNA damaging natural principles from several plants, including Alangium javanicum, Anisophyllea apetala, Crypteronia paniculata, Mouririi sp. and Scholtzia parviflora. Although none of the isolated principles mediated frank strand scission of DNA in vitro, all of them potently inhibited the growth of yeast in the absence of expression of RAD52.
Xu
Ya-ming
YM
Departments of Chemistry and Biology, University of Virginia, Charlottesville, VA 22901, USA. sidhecht@virginia.edu
Deng
Jing-Zhen
JZ
Ma
Ji
J
Chen
Shao-Nong
SN
Marshall
Rebekah
R
Jones
Shannon H
SH
Johnson
Randall K
RK
Hecht
Sidney M
SM
D001681:Biological Assay; D004249:DNA Damage / Q000187:drug effects*; D004278:DNA, Superhelical / Q000187:drug effects; D004610:Ellagic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology; D010944:Plants / Q000737:chemistry; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013329:Structure-Activity Relationship
D004278:DNA, Superhelical; D010936:Plant Extracts; D004610:Ellagic Acid