The antitumor agent bleomycin is believed to mediate its thera- peutic effects at the level of DNA strand scission; this process requires oxygen and an appropriate metal ion and proceeds via oxidative damage to the carbohydrate moiety of DNA. Metallobleamycins participate catalytically in DNA cleavage, apparently via the intermediacy of high valent metal-oxo complexes, which delivers a reactive form of oxygen to a DNA sugar subsequent to binding of the metallobleomycin to the DNA duplex. Also investigated were two structural series of natural products that have been shown for the first time to cleave DNA. One series, exemplified by (-)-epicatechin and procyanidin B2, was identified initially as constituents of Celastrus pringli Rose. Also studied was a series of 5-alkylresorcinols isolated from Hakea trifurcata. In common with blecmycin, DNA strand scission by both types of agents required a metal ion and O2. However, for both the flavanoids and 5-alkylresorcinols, DNA cleavage did not require any reductant and was actually diminished in the presence of thiols.
ASJC Scopus subject areas
- Chemical Engineering(all)