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

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