Inhibition of DNA-Topoisomerase I by Acylated Triterpene Saponins from Pittosporum angustifolium Lodd

doi:10.1007/s13659-016-0087-5

应用天然产物 ›› 2016, Vol. 6 ›› Issue (2): 141-147.DOI: 10.1007/s13659-016-0087-5

• Short communication • 上一篇

Inhibition of DNA-Topoisomerase I by Acylated Triterpene Saponins from Pittosporum angustifolium Lodd

Christian Bäcker¹, Malgorzata N. Drwal², Robert Preissner², Ulrike Lindequist¹

1. Department of Pharmaceutical Biology, Institute of Pharmacy, Ernst Moritz Arndt University Greifswald, Friedrich-LudwigJahn-Straße 17, 17489 Greifswald, Germany;
2. Structural Bioinformatics Group, Institute for Physiology, Charité-University Medicine Berlin, Lindenberger Weg 80, 13125 Berlin, Germany

收稿日期:2015-11-26 修回日期:2016-01-13 出版日期:2016-04-24 发布日期:2018-02-08
通讯作者: Christian Bäcker,e-mail:cbaecker@uni-greifswald.de
基金资助:
We sincerely thank Dr. R. Kunze for providing the plant material

Inhibition of DNA-Topoisomerase I by Acylated Triterpene Saponins from Pittosporum angustifolium Lodd

Christian Bäcker¹, Malgorzata N. Drwal², Robert Preissner², Ulrike Lindequist¹

1. Department of Pharmaceutical Biology, Institute of Pharmacy, Ernst Moritz Arndt University Greifswald, Friedrich-LudwigJahn-Straße 17, 17489 Greifswald, Germany;
2. Structural Bioinformatics Group, Institute for Physiology, Charité-University Medicine Berlin, Lindenberger Weg 80, 13125 Berlin, Germany

Received:2015-11-26 Revised:2016-01-13 Online:2016-04-24 Published:2018-02-08
Supported by:
We sincerely thank Dr. R. Kunze for providing the plant material

摘要/Abstract

摘要： 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.

关键词: Pittosporum angustifolium, Acylated triterpene saponins, Cytotoxicity, Topoisomerase I, Docking

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.

Key words: Docking, Pittosporum angustifolium, Acylated triterpene saponins, Cytotoxicity, Topoisomerase I

Christian Bäcker, Malgorzata N. Drwal, Robert Preissner, Ulrike Lindequist. Inhibition of DNA-Topoisomerase I by Acylated Triterpene Saponins from Pittosporum angustifolium Lodd[J]. 应用天然产物, 2016, 6(2): 141-147.

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Inhibition of DNA-Topoisomerase I by Acylated Triterpene Saponins from Pittosporum angustifolium Lodd

Inhibition of DNA-Topoisomerase I by Acylated Triterpene Saponins from Pittosporum angustifolium Lodd

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