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.Graphical AbstractTen 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.

Bioassay Guided Fractionation Protocol for Determining Novel Active Compounds in Selected Australian Flora

“…Notable values were also seen in BPF and TKF and GGL. High antioxidative capacity and total phenolic content often dictates the bioactive potential of a plant matrix [ 2 , 4 , 5 ]. Hence, it was postulated that KPF would show high bioactivity in the anticancer and antimicrobial bioassays.…”

Recent Advances in the Extraction of Pittosporum angustifolium Lodd. Used in Traditional Aboriginal Medicine: A Mini Review

“…IC 50 values were found to range between 2.8 and 46.5 µM, with most compounds having comparative or higher activities (2.8-8.6 µM) than the positive control camptothecin (7.4 µM). The study revealed the cytotoxic effect was caused only by the inhibition of topoisomerase I [9]. In a blind docking study, all triterpene saponins investigated were expected to display a similar binding mode to camptothecin.…”

“…Bäcker et al [9] further screened the isolated compounds (triterpene saponins) extracted from the Gumby Gumby plant for their cytotoxic potential against tumourigenic cell lines. The authors found evidence of triterpene saponins causing the inhibition of human topoisomerase I in a DNA relaxation assay.…”

“…Several bioactive compounds are found in most parts of P. angustifolium, from the leaves and seeds to the bark and root. The aerial components, which are exposed to air, including leaves, flowers, fruits, and stems, are utilised in traditional medicine to treat numerous different conditions [9]. A number of the bioactive compounds found in P. angustifolium are tabulated in Table 1.…”

Bioassay-Guided Fractionation of Pittosporum angustifolium and Terminalia ferdinandiana with Liquid Chromatography Mass Spectroscopy and Gas Chromatography Mass Spectroscopy Exploratory Study

“…When compared to the retention times of the predominant peaks in the chromatograms of the subfractions (Figure 6), only one peak at a Although numerous studies have identified triterpenoid saponins, terpenoids, phenols, and coumarin compounds isolated from P. angustifolium as having potential anticancer properties [10,17,18,35,36], only a few have been shown to be effective in vitro. Backer et al (2016) screened ten acylated saponins for their ability to inhibit human DNA-topoisomerase I, an enzyme responsible for resolving torsional stress associated with DNA replication, transcription, and chromatin condensation [37]. Inhibitors of DNA-topoisomerase I can inhibit the proliferation of cancer cells, and such agents are commonly used in chemotherapy for their antiproliferative effects.…”