Abstract
Bioassay-guided fractionation of extracts prepared from Brackenridgea nitida and Bleasdalea bleasdalei using an assay to detect DNA polymerase β inhibition, resulted in the isolation of the inhibitory principle, (24E)-3β-hydroxy-7,24-euphadien-26-oic acid (1), a new euphane triterpenoid. The structure of 1 was established on the basis of HRMS and 1D and 2D NMR spectroscopic methods and was confirmed further by X-ray crystallographic analysis. Compound 1 inhibited rat DNA polymerase β with an IC50 value of 23 μM in the presence of bovine serum albumin (BSA) and 9.7 μM in the absence of BSA, consistent with the possibility that 1 may be of utility in vivo. This possibility was further supported by the finding that 1 potentiated the inhibitory action of the anticancer drug bleomycin in cultured P-388D1 cells, reducing the number of viable cells by 48% when employed at a concentration of 25 μM in the presence of an otherwise nontoxic (75 nM) concentration of bleomycin. Compound 1 is the first euphane-type triterpenoid found to inhibit DNA polymerase β.
Original language | English (US) |
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Pages (from-to) | 1356-1360 |
Number of pages | 5 |
Journal | Journal of Natural Products |
Volume | 63 |
Issue number | 10 |
DOIs | |
State | Published - 2000 |
Externally published | Yes |
ASJC Scopus subject areas
- Analytical Chemistry
- Molecular Medicine
- Pharmacology
- Pharmaceutical Science
- Drug Discovery
- Complementary and alternative medicine
- Organic Chemistry