title: DNA topoisomerase I inhibitory alkaloids from Corydalis saxicola.
abstract: 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.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, P. R. China.
authors.forename: Xuanxuan
authors.initials: X
authors.lastname: Cheng
authors.forename: Dongmei
authors.initials: D
authors.lastname: Wang
authors.forename: Lin
authors.initials: L
authors.lastname: Jiang
authors.forename: Depo
authors.initials: D
authors.lastname: Yang
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000302:isolation & purification / Q000494:pharmacology; D031311:Corydalis / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D019906:Nuclear Magnetic Resonance, Biomolecular; D059004:Topoisomerase I Inhibitors
chemical_list: D000470:Alkaloids; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors