Synthesis and biological evaluation of phenyl substituted polyoxygenated xanthone derivatives as anti-hepatoma agents

Dai, Ming; Xing, Yuan; Kang, Jian; Zhu, Zhengyan; Yue, Rongcai; Hu, Yuan; Chen, Bingyang; Zhang, Wei‐Dong; Liu, Runhui; Sun, Qian

doi:10.1016/j.ejmech.2013.08.020

Cited by 11 publications

(11 citation statements)

References 31 publications

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“…For ISJ synthesis, the construction of the xanthone nucleus and the benzopyran ring were performed based on our previous work 33 34 . The retrosynthetic analysis of ISJ is outlined in Fig.…”

Section: Resultsmentioning

confidence: 99%

“…In our previous studies, a new series of derivatives of phenyl-substituted polyoxygenated xanthone were synthesized and evaluated for in vitro cytotoxicity against HCC cells and hepatocytes 33 34 . In the present study, ISJ and compound 7 demonstrated potency at several cellular-level activities, thereby supporting the derivatives’ antitumor effects.…”

Section: Discussionmentioning

confidence: 99%

“…The cell viability assay was performed as previously reported using a Cell Counting Kit-8 (CCK-8; Dojindo, Kumamoto, Japan) 33 34 . The relative cell viability was presented as % inhibition and calculated using the following formula:…”

Section: Methodsmentioning

confidence: 99%

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Inhibition of protein kinase C by isojacareubin suppresses hepatocellular carcinoma metastasis and induces apoptosis in vitro and in vivo

Xing

Chen

et al. 2015

Sci Rep

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Targeted inhibition of protein kinase C (PKC) inhibits hepatocellular carcinoma (HCC) proliferation and metastasis. We previously reported the cytotoxicity of a series of synthetic phenyl-substituted polyoxygenated xanthone derivatives against human HCC. In the current study, the most potent natural product, isojacareubin (ISJ), was synthesized, and its cellular-level antihepatoma activities were evaluated. ISJ significantly inhibited cell proliferation and was highly selective for HCC cells in comparison to nonmalignant QSG-7701 hepatocytes. Moreover, ISJ exhibited pro-apoptotic effects on HepG2 hepatoma cells, as well as impaired HepG2 cell migration and invasion. Furthermore, ISJ was a potent inhibitor of PKC, with differential actions against various PKC isotypes. ISJ selectively inhibited the expression of aPKC (PKCζ) in the cytosol and the translocation of cytosolic PKCζ to membrane site. ISJ also directly interacted with cPKC (PKCα) and nPKC (PKCδ, PKCε and PKCμ) and thereby inhibited the early response of major MAPK phosphorylation and the late response of HCC cell invasion and proliferation. In a hepatoma xenograft model, ISJ pretreatment resulted in significant antihepatoma activity in vivo. These findings identify ISJ as a promising lead compound for the development of new antihepatoma agents and may guide the search for additional selective PKC inhibitors.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Inhibition of protein kinase C by isojacareubin suppresses hepatocellular carcinoma metastasis and induces apoptosis in vitro and in vivo

Xing

Chen

et al. 2015

Sci Rep

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“…However, the mechanism of action of H 2 S in the development of NAFLD has not been fully investigated. Human liver cells L02 and QSG-7701 are widely used to determine the therapeutic effects of new donors/drugs (Dai et al, 2013;Wu et al, 2017a). OA, a mono-unsaturated fatty acid (FA), and palmitic acid (PA), a saturated FA, are two main dietary FAs (Liu et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Hydrogen Sulfide Attenuates High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease by Inhibiting Apoptosis and Promoting Autophagy via Reactive Oxygen Species/Phosphatidylinositol 3-Kinase/AKT/Mammalian Target of Rapamycin Signaling Pathway

Zhong

Wang

et al. 2020

Front. Pharmacol.

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Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide. Hydrogen sulfide (H2S) is involved in a wide range of physiological and pathological processes. Nevertheless, the mechanism of action of H2S in NAFLD development has not been fully clarified. Here, the reduced level of H2S was observed in liver cells treated with oleic acid (OA). Administration of H2S increased the proliferation of OA-treated cells. The results showed that H2S decreased apoptosis and promoted autophagy through reactive oxygen species (ROS)-mediated phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) cascade in OA-treated cells. In addition, administration of H2S relieved high-fat diet (HFD)-induced NAFLD via inhibition of apoptosis and promotion of autophagy. These findings suggest that H2S could ameliorate HFD-induced NAFLD by regulating apoptosis and autophagy through ROS/PI3K/AKT/mTOR signaling pathway. Novel H2S-releasing donors may have therapeutic potential for the treatment of NAFLD.

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“…A series of xanthone analogues were reported and demonstrated improved in vitro antitumor activity versus the parent xanthone and drug-like properties 13,14. For example, a caged xanthone (Figure 1B; IC 50 = 3.60 μM for A549 cells) was synthesized using the prenyl moiety of its parent xanthone,15,16 while 3-phenylxanthone (Figure 1C; IC 50 = 6.27 μM for QGY-7703 cells) was identified as a potent and promising antitumor agent 17Figure 1Chemical structures of xanthones ( A ) Basic structure of xanthone, ( B, C ) Derivatives of xanthone.…”

Section: Introductionmentioning

confidence: 99%

<p>Synthesis of Novel Xanthone Analogues and Their Growth Inhibitory Activity Against Human Lung Cancer A549 Cells</p>

Dai

Zhang

et al. 2019

DDDT

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PurposeXanthones demonstrated an array of pharmacological activities via non-covalent DNA interaction and have been widely utilized in new drug research. The introduction of the polar 1,2,3-triazole ring located at the C3-position of xanthone has not been reported thus far.MethodsIn the present study, a series of xanthone derivatives were designed, synthesized, and characterized through 1H NMR, 13C NMR, and MS. The methyl thiazolyl tetrazolium method was used to evaluate the cytotoxic activity of compounds. Furthermore, the structure–activity relationship and the potential mechanism of target compounds were investigated.ResultsThe IC50 showed that the inhibitory activity of 18 target compounds was higher than that of the original xanthone intermediate 4. In particular, compound 1j was the most active agent against A549 cancer cells (IC50 = 32.4 ± 2.2 μM). Moreover, apoptosis analysis indicated different contributions of early/late apoptosis to cell death for compounds 1h and 1j. The results of Western blotting analysis showed that compound 1j significantly increased the expression of caspase 3, Bax, and c-Jun N-terminal kinase, and regulated p53 to a better healthy state in cancer cells.ConclusionWe synthesized several derivatives of xanthone and evaluated their cytotoxicity. The evidence suggested that compound 1j possessed greater anticancer potential for further evaluations.

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Synthesis and biological evaluation of phenyl substituted polyoxygenated xanthone derivatives as anti-hepatoma agents

Cited by 11 publications

References 31 publications

Inhibition of protein kinase C by isojacareubin suppresses hepatocellular carcinoma metastasis and induces apoptosis in vitro and in vivo

Inhibition of protein kinase C by isojacareubin suppresses hepatocellular carcinoma metastasis and induces apoptosis in vitro and in vivo

Hydrogen Sulfide Attenuates High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease by Inhibiting Apoptosis and Promoting Autophagy via Reactive Oxygen Species/Phosphatidylinositol 3-Kinase/AKT/Mammalian Target of Rapamycin Signaling Pathway

<p>Synthesis of Novel Xanthone Analogues and Their Growth Inhibitory Activity Against Human Lung Cancer A549 Cells</p>

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