Biomedical subjects
Publications and source records attributed to Rebekah Marshall.
An organic extract prepared from Rinorea anguifera was investigated in order to identify the natural principle(s) responsible for stabilization of a topoisomerase I-DNA covalent binary complex. Bioassay-guided fractionation resulted in the isolation of mauritianin and (+)-syringaresinol as new topoisomerase I inhibitors, and also of the known inhibitor camptothecin.
Bioassay-guided fractionation of an active organic extract of Piper caninum, using a sensitive yeast assay to monitor putative double-strand DNA-damaging activity, resulted in the isolation of the 4,5-dioxoaporphine alkaloid cepharadione A (1). Compound 1 exhibited potent inhibitory activity in a yeast cytotoxicity assay with IC(50) values of 50.2 nM toward RS321NpRAD52 grown on glucose versus 293 nM toward the same yeast strain grown on galactose.
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.
A survey of crude plant extracts using a new yeast strain designed to identify DNA-damaging agents resulted in the identification of an extract prepared from Crypteronia paniculata. Bioassay-guided fractionation resulted in the isolation of three active compounds. Two of these were ellagic acid derivatives, namely, 3,3'-di-O-methylellagic acid 4'-O-beta-d-xylopyranoside (1) and 3'-O-methyl-3,4-methylenedioxyellagic acid 4'-O-beta-d-glucopyranoside (2). The third was identified as kaempferol-3-O-alpha-l-rhamnoside (3). The three principles exhibited strong, selective cytotoxity toward the RAD52 repair-deficient yeast strain.