Synthesis of reduced xanthatin derivatives and<i>in vitro</i>evaluation of their antifungal activity

Pinel, Benoit; Landreau, Anne; Séraphin, Denis; Larcher, Gérald; Bouchara, Jean‐Philippe; Richomme, Pascal

doi:10.1080/14756360500213231

Cited by 14 publications

(10 citation statements)

References 27 publications

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“…(Asteraceae), a native herb commonly used in China [ 4 , 5 ]. Previous studies demonstrated that xanthatin exhibits a wide variety of bioactivities, including anticancer [ 6 , 7 ], antiangiogenesis [ 8 – 10 ], antiviral [ 10 ], antiinflammatory [ 11 ], antifungal [ 12 , 13 ], antibacterial [ 14 ], antitrypanosome [ 11 ], and antileishmanial [ 13 ] activities. In addition, xanthatin was reported to suppress proliferation and induce apoptosis in a wide variety of cancer cell culture systems, including non-small cell lung cancer cells (A549 and H522 cells), MKN-45 human gastric carcinoma cells, MDA-MB-231 human breast cancer cells, B16-F10 murine melanoma cells, and L1210 mouse leukemia cells [ 9 , 10 , 15 – 23 ].…”

Section: Introductionmentioning

confidence: 99%

Xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating endoplasmic reticulum stress-dependent CHOP pathway

Cao

et al. 2019

Acta Pharmacol Sin

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Xanthatin is a natural sesquiterpene lactone purified from Xanthium strumarium L. , which has shown prominent antitumor activity against a variety of cancer cells. In the current study, we investigated the effect of xanthatin on the growth of glioma cells in vitro and in vivo, and elucidated the underlying mechanisms. In both rat glioma C6 and human glioma U251 cell lines, xanthatin (1–15 μM) dose-dependently inhibited cell viability without apparent effect on the cell cycle. Furthermore, xanthatin treatment dose-dependently induced glioma cell apoptosis. In nude mice bearing C6 glioma tumor xenografts, administration of xanthatin (10, 20, 40 mg·kg −1 ·d −1 , ip, for 2 weeks) dose-dependently inhibited the tumor growth, but did not affect the body weight. More importantly, xanthatin treatment markedly increased the expression levels of the endoplasmic reticulum (ER) stress-related markers in both the glioma cell lines as well as in C6 xenografts, including glucose-regulated protein 78, C/EBP-homologous protein (CHOP), activating factor 4, activating transcription factor 6, spliced X-box binding protein-1, phosphorylated protein kinase R-like endoplasmic reticulum kinase, and phosphorylated eukaryotic initiation factor 2a. Pretreatment of C6 glioma cells with the ER stress inhibitor 4-phenylbutyric acid (4-PBA, 7 mM) or knockdown of CHOP using small interfering RNA significantly attenuated xanthatin-induced cell apoptosis and increase of proapoptotic caspase-3. These results demonstrate that xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating the ER stress-related unfolded protein response pathway involving CHOP induction. Xanthatin may serve as a promising agent in the treatment of human glioma.

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Section: Introductionmentioning

confidence: 99%

Xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating endoplasmic reticulum stress-dependent CHOP pathway

Cao

et al. 2019

Acta Pharmacol Sin

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“…It was also shown to have in vitro anticancer activities in human colon (WiDr cells) and breast (MDA‐MB‐231) cancer cells (Ramírez‐Erosa et al , ). In other studies, xanthatin showed bactericidal and fungicidal activities and its biological effects were correlated with the α‐methylene‐γ‐lactone part of its chemical structure (Ginesta‐Perls et al , ; Pinel et al , ). 8‐Epi‐xanthatin and 8‐epi‐xanthatin epoxide, which are the epimers of xanthatin, disturbed insect development (Kawazu et al , ), and showed antimalarial (Joshi et al , ), anti‐farnesyltransferase and cytotoxic properties (Kim et al , ).…”

Section: Discussionmentioning

confidence: 92%

Biological Activities of Xanthatin from Xanthium strumarium Leaves

Nibret

Youns

Krauth‐Siegel

2011

Phytotherapy Research

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The objective of the present work was to evaluate the biological activities of the major bioactive compound, xanthatin, and other compounds from Xanthium strumarium (Asteraceae) leaves. Inhibition of bloodstream forms of Trypanosoma brucei brucei and leukaemia HL-60 cell proliferation was assessed using resazurin as a vital stain. Xanthatin was found to be the major and most active compound against T. b. brucei with an IC(50) value of 2.63 µg/mL and a selectivity index of 20. The possible mode of action of xanthatin was further evaluated. Xanthatin showed antiinflammatory activity by inhibiting both PGE(2) synthesis (24% inhibition) and 5-lipoxygenase activity (92% inhibition) at concentrations of 100 µg/mL and 97 µg/mL, respectively. Xanthatin exhibited weak irreversible inhibition of parasite specific trypanothione reductase. Unlike xanthatin, diminazene aceturate and ethidium bromide showed strong DNA intercalation with IC(50) values of 26.04 µg/mL and 44.70 µg/mL, respectively. Substantial induction of caspase 3/7 activity in MIA PaCa-2 cells was observed after 6 h of treatment with 100 µg/mL of xanthatin. All these data taken together suggest that xanthatin exerts its biological activity by inducing apoptosis and inhibiting both PGE(2) synthesis and 5-lipoxygenase activity thereby avoiding unwanted inflammation commonly observed in diseases such as trypanosomiasis.

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“…The sesquiterpene lactone xanthatin is the major bioactive compound isolated from the leaves of Xanthium sibiricum. Xanthatin has beneficial biological activities such as antitumor, antifungal, and antiplasmodial effects [119][120][121]. Xanthatin was also shown to have antiangiogenic properties through the inhibition of the VEGFR2 signaling pathways [122].…”

Section: Non-flavonoid Phytochemicalsmentioning

confidence: 99%

Pharmacological Potential of Small Molecules for Treating Corneal Neovascularization

2020

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Under healthy conditions, the cornea is an avascular structure which allows for transparency and optimal visual acuity. Its avascular nature is maintained by a balance of proangiogenic and antiangiogenic factors. An imbalance of these factors can result in abnormal blood vessel proliferation into the cornea. This corneal neovascularization (CoNV) can stem from a variety of insults including hypoxia and ocular surface inflammation caused by trauma, infection, chemical burns, and immunological diseases. CoNV threatens corneal transparency, resulting in permanent vision loss. Mainstay treatments of CoNV have partial efficacy and associated side effects, revealing the need for novel treatments. Numerous natural products and synthetic small molecules have shown potential in preclinical studies in vivo as antiangiogenic therapies for CoNV. Such small molecules include synthetic inhibitors of the vascular endothelial growth factor (VEGF) receptor and other tyrosine kinases, plus repurposed antimicrobials, as well as natural source-derived flavonoid and non-flavonoid phytochemicals, immunosuppressants, vitamins, and histone deacetylase inhibitors. They induce antiangiogenic and anti-inflammatory effects through inhibition of VEGF, NF-κB, and other growth factor receptor pathways. Here, we review the potential of small molecules, both synthetics and natural products, targeting these and other molecular mechanisms, as antiangiogenic agents in the treatment of CoNV.

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Synthesis of reduced xanthatin derivatives andin vitroevaluation of their antifungal activity

Abstract: The synthesis of new xanthanolide derivatives is reported starting from xanthatin, a sesquiterpenic lactone isolated from Xanthium macrocarpum (Asteraceae). In vitro evaluation of their antifungal activity has been investigated.

Cited by 14 publications

References 27 publications

Xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating endoplasmic reticulum stress-dependent CHOP pathway

Xanthatin induces glioma cell apoptosis and inhibits tumor growth via activating endoplasmic reticulum stress-dependent CHOP pathway

Biological Activities of Xanthatin from Xanthium strumarium Leaves

Pharmacological Potential of Small Molecules for Treating Corneal Neovascularization

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