title: Inhibition of DNA-Topoisomerase I by Acylated Triterpene Saponins from Pittosporum angustifolium Lodd.
abstract: Previous phytochemical investigation of the leaves and seeds of Pittosporum angustifolium Lodd. led to the isolation and structural elucidation of polyphenols and triterpene saponins. Evaluation for cytotoxicity of isolated saponins revealed that the predominant structural feature for a cytotoxic activity are acyl substituents at the oleanane aglycon backbone. The present work reports the results of a screening of 10 selected acylated saponins for their potential to inhibit the human DNA-topoisomerase I, giving rise to IC50 values in a range of 2.8-46.5 µM. To clarify the mode of observed cytotoxic action and, moreover, to distinguish from a pure surfactant effect which is commonly accompanied with saponins, these results indicate an involvement of the topoisomerase I and its role as a possible target structure for a cytotoxic activity. In addition, computational predictions of the fitting of saponins to the topoisomerase I-DNA complex, indicate a similar binding mode to that of clinically used topoisomerase I inhibitors. Ten acylated triterpene saponins from Pittosporum angustifolium were investigated for their potential to inhibit the human DNA-topoisomerase I and computational predictions of the fitting of saponins to the topoisomerase I-DNA complex were carried out.
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy, Ernst Moritz Arndt University Greifswald, Friedrich-Ludwig-Jahn-Straße 17, 17489, Greifswald, Germany. cbaecker@uni-greifswald.de.
authors.forename: Christian
authors.initials: C
authors.lastname: Bäcker
authors.affiliation: Structural Bioinformatics Group, Institute for Physiology, Charité - University Medicine Berlin, Lindenberger Weg 80, 13125, Berlin, Germany.
authors.forename: Malgorzata N
authors.initials: MN
authors.lastname: Drwal
authors.affiliation: Structural Bioinformatics Group, Institute for Physiology, Charité - University Medicine Berlin, Lindenberger Weg 80, 13125, Berlin, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Preissner
authors.affiliation: Department of Pharmaceutical Biology, Institute of Pharmacy, Ernst Moritz Arndt University Greifswald, Friedrich-Ludwig-Jahn-Straße 17, 17489, Greifswald, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Lindequist
keywords: Acylated triterpene saponins; Cytotoxicity; Docking; Pittosporum angustifolium; Topoisomerase I