Cytotoxic Guanidine Alkaloids from Pterogyne nitens (original) (raw)
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Planta Medica, 2021
The common fern, bracken (Pteridium aquilinum), is well known for its toxic effects on livestock due principally to the carcinogenic constituent ptaquiloside ( 1), although other toxins are present including the cyanogenic glycoside, prunasin ( 2). Here, we report an improved and relatively “green” process for the isolation of 1 and 2 from fresh bracken fronds and the evaluation of 1 for cytotoxicity against several cancer cell lines. The results indicate that 1 displays selective toxicity against cancer cells relative to noncancer retinal epithelial cells, and the improved method for the isolation of 1 is expected to facilitate further exploration of its pharmacological properties.
Reduced pteridine derivatives induce apoptosis in PC12 cells
Neurochemistry International, 2002
In cerebrospinal fluid of patients with cerebral infections, elevated concentrations of the pteridine compounds neopterin and 7,8-dihydroneopterin were detected. Here, the potential of pteridines to induce apoptosis of the rat pheochromocytoma cells (PC12) was investigated. In contrast to aromatic pteridines like neopterin, the reduced forms 7,8-dihydroneopterin, 5,6,7,8-tetrahydrobiopterin and 7,8-dihydrobiopterin led to a significant increase of apoptotic cells. After terminal differentiation, cells were less sensitive to incubation with pteridines. A noticeable augmentation of apoptosis was observed upon incubation with 7,8-dihydroneopterin and 7,8-dihydrofolic acid. Antioxidants partly protected PC12 cells from pteridine-induced apoptosis, suggesting the involvement of reactive oxygen intermediates. Exposure of cells to 7,8-dihydroneopterin led to activation of the mitogen-activated protein (MAP) kinase and to a lesser degree also of JUN/SAP kinase. Results implicate that high concentrations of reduced pteridines, might contribute to the pathogenesis involved in neurodegeneration.
Antiproliferative effect of Pterogyne nitens on melanoma cells
2009
As part of our program of bioprospecting for novel antitumor drug prototypes, twenty extracts and fractions obtained from Pterogyne nitens Tul. (Fabaceae, Caesalpinioideae) were screened for antiproliferative activity against B16F10 murine melanoma cells, by the MTT colorimetric assay. The strongest activity was found in EtOAc fractions from the flowers (IC 50 = 0.35 µg/mL), fruits (IC 50 = 0.34 µg/mL), leaves (IC 50 = 0.33 µg/mL) and stems (IC 50 = 0.29 µg/mL). Analysis by TLC and HPLC-DAD showed the presence of guanidine alkaloids, flavones and flavonols in the bioactive samples. Additionally, a phytochemical study of the EtOAc fraction of the stems afforded quercetin (1) and isoquercitrin (2), two flavonols with antiproliferative activity previously described in the literature. On the basis of these results, it can be concluded that P. nitens inhibits the growth of melanoma cells in vitro. Further investigations will be needed to assess the usefulness of the samples under study for the treatment of neoplasms and to characterize other bioactive compounds.
Proceedings of the Japan Academy. Ser. B: Physical and Biological Sciences, 2000
We have noticed the presence of cytotoxic activity in the body fluid of a butterfly, Ideopsis similis, in family Danaidae. The cytotoxic principles were purified and identified to be phenanthroindolizidine alkaloids. In addition, the cytotoxic activity was observed in the leaves of Tylophora tanakae, which is a host plant for caterpillars of I. similis. In the present study, cytotoxic principles in methanol extracts of the leaves against human gastric carcinoma TMK-1 cells were purified by acid-base partition, repeated HPLC and preparative TLC, and two cytotoxic compounds were isolated. From spectroscopic analysis of their structures, they were identified as phenanthroindolizidine alkaloids, traps-(+)-3,14a dihydroxy-4,6,7-trimethoxyphenanthroindolizidine N-oxide and (-)-7-hydroxy-2,3,6-trimethoxyphenanthroindolizidine. The amounts of two compounds isolated from 200 g of dried leaves were 3.5 and 4.0 mg, respectively. These alkaloids are different from those in the fluid of I. similis. When TMK-1 cells were treated with these phenanthroindolizidine alkaloids, strong cytotoxic effects were observed, doses of 6 ng/ml for traps-(+)-3,14a-dihydroxy-4,6,7-trimethoxyphenanthroindolizidine N-oxide and 3 ng/ml for (-)-7hydroxy-2,3,6-trimethoxyphenanthroindolizidine inducing 50% cell growth inhibition (IC5o).
Purification of ptaquiloside, a carcinogen from Pteridium aquilinum
Phytochemistry, 1995
Ptaquiloside, the major carcinogen of bracken fern (Pteridium aquilinum), was isolated in high yield from milled freeze-dried plant material. Because the compound is unstable, a new method was devised to avoid steps which caused loss of activity. Modern multipulse and 2D NMR techniques allowed confirmation of the previously proposed structure, although some assignments were shown to be incorrect.
Antigenotoxic, Antioxidant and Lymphocyte Induction Effects Produced by Pteropodine
Basic & Clinical Pharmacology & Toxicology, 2009
Abstract: Pteropodine is a heterohimbine-type oxindole alkaloid specifically isolated from ‘Cat's claw’ (Uncaria tomentosa), a plant that has shown cytostatic, anti-inflammatory and antimutagenic properties and is used in traditional medicine to cure a number of diseases. In this report, we studied the ability of pteropodine to decrease the rate of sister-chromatid exchanges and micronucleated polychromatic erythrocytes in mice administered doxorubicin. We also determined its capacity to induce lymphocyte production in mice as well as its free radical scavenging potential by applying the DPPH assay. We found pteropodine (100–600 mg/kg) to significantly decrease the frequency of sister-chromatid exchanges and micronucleated polychromatic erythrocytes in mice administered with 10 mg/kg of doxorubicin. Furthermore, we determined that pteropodine partially corrected bone marrow cytotoxicity induced by doxorubicin, as it showed an improvement in the rate of polychromatic erythrocytes. Besides, 600 mg/kg of pteropodine increased 25.8% of the production of lymphocytes over the control value along a 96-hr assay, and it exhibited a strong capacity to trap the DPPH-free radical (98.26% with 250 µg/ml). Our results establish that pteropodine is an effective antimutagen in the model used, and suggest that pteropodine deserves further research in the area of cell protective potential and its mechanism of action.
Ptaquiloside‑induced cytotoxicity in Crandall feline kidney and HGC‑27 cells
Oncology Letters, 2014
Ptaquiloside (PTA) is a potent genotoxic carcinogenic compound, which is found in bracken ferns and predominantly causes gastric tumors in humans, as well as bladder tumors and chronic enzootic hematuria in cattle. The underlying molecular mechanisms of PTA remain a topic for interdisciplinary investigation. The aim of the present study was to determine the possible cytotoxic effect of 24 h of PTA exposure in Crandall feline kidney (CrFK) and human gastric cells (the HGC-27 cell line) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactose dehydrogenase (LDH) analysis. The cytotoxic effects of PTA (0.0005-500 µg/ml) were found to increase in a dose-dependent manner, whereby the half maximal inhibitory concentration values were 11.17 and 11.86 µg/ml in the CrFK cells, and 2.03 and 2.56 µg/ml in the HGC-27 cells, by LDH and MTT assay, respectively. The results of the present study are consistent with those of previous studies associated with the cytotoxicity of PTA; however, cytotoxicity was identified to occur at significantly lower doses. This cytotoxic effect in vitro at particularly high doses may be linked to the initiation of carcinogenesis as a result of oxidative stress.
Reduced Pteridine Derivatives Induce Apoptosis in Human Neuronal NT2/HNT Cells
Immunobiology, 2000
Elevated concentrations of the pteridine compound neopterin, usually accompanied by 7,8dihydroneopterin were found in cerebrospinal fluids of patients with neurodegenerative diseases and central nervous system infections. Here, the potential of pteridines to induce apoptosis of the human neuronal cell line (NT2) was investigated. Reduced neopterin, biopterin-and folate derivatives led to a time-dependent increase of apoptosis of cells. In contrast, non-reduced pteridines did not significantly alter cell survival. After differentiation of neuronal precursor cells to neurons and astrocyte-like cells, similar effects were detected. Antioxidants partly protected NT2 from pteridines-induced apoptosis, suggesting the involvement of reactive oxygen intermediates. In vitro experiments using dichlorofluorescin-diacetate further indicated a direct formation of reactive oxygen species in cells. Results implicate that high concentrations of reduced pteridines, might contribute to the loss of neuronal cells in neurodegenerative diseases. Abbreviations: IFN-y =interferon-y; GTP =guanosine triphosphate; H 2 0 2 =hydrogen peroxide.