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DNA Topoisomerase I Inhibitory Alkaloids from Corydalis saxicola
Author(s) -
Cheng Xuanxuan,
Wang Dongmei,
Jiang Lin,
Yang Depo
Publication year - 2008
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.200890121
Subject(s) - topoisomerase , chemistry , alkaloid , camptothecin , topoisomerase inhibitor , biochemistry , dna , enzyme , isoquinoline , stereochemistry
Chemical studies of the Chinese herb Corydalis saxicola Bunting led to the isolation and identification of 14 alkaloids, 1 – 14 . Seven of these compounds, 4 – 9 and 11 , were obtained from this plant for the first time. Feruloylagmatine ( 7 ) is the first guanidine‐type alkaloid to be identified in the family Papaveraceae and in dicotyledonous plants. All of the isolated compounds were assayed for inhibitory activity against human DNA topoisomerase I. A DNA cleavage assay demonstrated that these alkaloids specifically inhibit topoisomerase through stabilization of the enzyme–DNA complex. Among the isolated alkaloids, (−)‐pallidine ( 8 ) and (−)‐scoulerine ( 11 ) showed strong inhibitory activities toward topoisomerase I that were comparable to camptothecin, a typical topoisomerase I inhibitor. A preliminary structure–activity relationship study suggested that the quaternary ammonium ion might play an important role in topoisomerase I inhibition by the isoquinoline alkaloids. These data indicated that DNA topoisomerase I inhibition represents probably one of the anticarcinogenic mechanisms of C. saxicola.