Inhibitors of DNA Topoisomerase I and II Isolated from theCoptisRhizomes

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Abstract
A water extract of Coptis chinensis was found to have the ability to stabilize the cleavable complex with mammalian DNA topoisomerase I. As the result of bioassay-guided fractionation, two protoberberine alkaloids, epiberberine and groenlandicine, were identified as active principles with topoisomerase I-mediated DNA cleavage activity in vitro. These two alkaloids did not induce topoisomerase II-mediated DNA cleavage. During further examination of the structurally related protoberberine alkaloids, berberrubine which is produced during the processing of Coptis rhizome as traditional medicine, was identified as a specific inducer of topoisomerase II-mediated DNA cleavage in vitro. These results indicated that protoberberine alkaloids are a chemical family which can induce cleavable complexes with topoisomerases I and II.

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