Design, synthesis and biological activities of tetrandrine and fangchinoline derivatives as antitumer agents

Li, Dechao; Liu, Haizheng; Liu, Yufa; Zhang, Qikun; Liu, Chao; Zhao, Shuhua; Jiang, Bo

doi:10.1016/j.bmcl.2016.12.029

Cited by 19 publications

(10 citation statements)

References 15 publications

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“…[ 114 ] Additionally, a tetrandrine derivative compound can reportedly exhibit significant cytotoxic effects and suppress the proliferation of HepG2 and MCF‐7 cells, with IC 50 values in the region of 16.06 and 25.41 μ m , respectively. [ 135 ] 5‐FU also displays a stronger inhibitory effect on cell survival in colon cancer HCT116 cells in the presence of tetrandrine (ranging 2.5 from 10 μ m ) and significantly suppresses cell proliferation and survival at a dose as low as 10 μ m when in the presence of 5 μ m tetrandrine, which is markedly lower than the IC 50 for 5‐FU in HCT116 cells. [ 83 ] Similar results have been acquired from an MTT proliferation assay, in which 5‐FU at a concentration as low as 2.5 μ m and in the presence of tetrandrine at or below 5 μ m can inhibit HCT116 cell proliferation significantly, suggesting that tetrandrine might exert synergistic effects when applied alongside other chemotherapy drugs.…”

Section: The Anticancer Activity Of Tetrandrinementioning

confidence: 99%

Tetrandrine: a review of its anticancer potentials, clinical settings, pharmacokinetics and drug delivery systems

Luan

Zeng

2020

Journal of Pharmacy and Pharmacology

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Objectives Tetrandrine, a natural bisbenzylisoquinoline alkaloid, possesses promising anticancer activities on diverse tumours. This review provides systematically organized information on cancers of tetrandrine in vivo and in vitro, discuss the related molecular mechanisms and put forward some new insights for the future investigations. Key findings Anticancer activities of tetrandrine have been reported comprehensively, including lung cancer, colon cancer, bladder cancer, prostate cancer, ovarian cancer, gastric cancer, breast cancer, pancreatic cancer, cervical cancer and liver cancer. The potential molecular mechanisms corresponding to the anticancer activities of tetrandrine might be related to induce cancer cell apoptosis, autophagy and cell cycle arrest, inhibit cell proliferation, migration and invasion, ameliorate metastasis and suppress tumour cell growth. Pharmaceutical applications of tetrandrine combined with nanoparticle delivery system including liposomes, microspheres and nanoparticles with better therapeutic efficiency have been designed and applied encapsulate tetrandrine to enhance its stability and efficacy in cancer treatment. Summary Tetrandrine was proven to have definite antitumour activities. However, the safety, bioavailability and pharmacokinetic parameter studies on tetrandrine are very limited in animal models, especially in clinical settings. Our present review on anticancer potentials of tetrandrine would be necessary and highly beneficial for providing guidelines and directions for further research of tetrandrine.

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Section: The Anticancer Activity Of Tetrandrinementioning

confidence: 99%

Tetrandrine: a review of its anticancer potentials, clinical settings, pharmacokinetics and drug delivery systems

Luan

Zeng

2020

Journal of Pharmacy and Pharmacology

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“…Tet and Fangchinoline (Fcn) are the two main bis-benzylisoquinoline alkaloids that exist in the plants of Stephania tetrandra. The structures of both Tet and Fcn are similar, but Fcn was reported to be associated with the inhibition of acetylcholinesterase and glutamate release in neurological diseases [7][8][9]. Fcn is a potent antioxidant, showing protective effects in oxidative cell injury [10].…”

Section: Introductionmentioning

confidence: 99%

Fangchinoline Induces Apoptosis, Autophagy and Energetic Impairment in Bladder Cancer

Fan¹,

Zhang²,

Ma³

et al. 2017

Cell Physiol Biochem

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Key Words Bladder cancer • Fangchinoline • Autophagy • Apoptosis • ProliferationAbatract Background/Aims: Tetrandrine and Fangchinoline (Fcn) are two natural products that are found in Stephania tetrandra. Tetrandrine is a known anti-bladder cancer compound, but the effects of Fcn on bladder cancer have been previously unclear. In the present study, we focused on the anti-tumor effects of Fcn on bladder cancer. Methods and Results: We treated T24 and 5637 bladder cancer cell lines with Fcn in vitro. We observed that Fcn inhibited the viability of bladder cancer cells in a concentration-dependent manner. The expression of PCNA, a biomarker of proliferation, was down-regulated. Fcn treatment induced both apoptosis and autophagy in bladder cancer cells, as shown by the increased cleavage of caspase-3, an upregulated LC3-II/LC3-I ratio and the down-regulated p62 level. Blocking autophagy with 3-MA (3-Methyladenine) enhanced Fcn-induced apoptosis, indicating that Fcn-induced autophagy was adaptive. Additionally, we observed that Fcn treatment inhibited mTOR and reduced the intracellular ATP levels. The exogenous addition of methyl pyruvate (MP) to compensate metabolic substrates alleviated Fcn-induced apoptosis and autophagy. Conclusions: Our data indicated that Fcn caused an impairment in energy generation, which led to apoptosis and adaptive autophagy in bladder cancer. These results demonstrated that Fcn may be a potential candidate for use in the prevention and treatment of bladder cancer.

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“…Previous studies demonstrated that dimethylated tetrandrine shares similar pharmacological activities with the parent drug tetrandrine 46-48. In this work, the demethylated tetrandrine is generated following the exposure of tetrandrine and reaches the maximum concentration 4 h after injection ( Figure S8C ).…”

Section: Resultsmentioning

confidence: 57%

Quantitative MALDI Imaging of Spatial Distributions and Dynamic Changes of Tetrandrine in Multiple Organs of Rats

et al. 2019

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Detailed spatio-temporal information on drug distribution in organs is of paramount importance to assess drug clinically-relevant properties and potential side-effects. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) as a label-free and sensitive imaging modality provides an additional means of accurately visualizing drug and its metabolites distributions in tissue sections. However, technical limitations, complex physiochemical environment of surface and low abundance of target drugs make quantitative MALDI imaging of drug and its metabolites quite challenging. Methods : In this study, an internal standard correction strategy was applied for quantitative MALDI imaging of tetrandrine in multiple organs of rats including lung, liver, kidney, spleen, and heart. The feasibility and reliability of the developed quantitative MSI method were validated by conventional liquid chromatography-tandem MS (LC-MS/MS) analysis, and the two methods showed a significant correlation. Results : The quantitative MALDI imaging method met the requirements of specificity, sensitivity and linearity. Tissue-specific spatio-temporal distribution patterns of tetrandrine in different organs were revealed after intravenous administration in the rat. Moreover, demethylated metabolite was detected in liver tissues. Conclusions : The current work illustrates that quantitative MALDI imaging provides an alternative means of accurately addressing the problem of drug and its metabolites distribution in tissues, complementary to traditional LC-MS/MS of tissue homogenates and whole-body autoradiography (WBA). Quantitative spatio-chemical information obtained here can improve our understanding of pharmacokinetics (PK), pharmacodynamics (PD), and potential transient toxicities of tetrandrine in organs, and possibly direct further optimization of drug properties to reduce drug-induced organ toxicity.

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Design, synthesis and biological activities of tetrandrine and fangchinoline derivatives as antitumer agents

Cited by 19 publications

References 15 publications

Tetrandrine: a review of its anticancer potentials, clinical settings, pharmacokinetics and drug delivery systems

Tetrandrine: a review of its anticancer potentials, clinical settings, pharmacokinetics and drug delivery systems

Fangchinoline Induces Apoptosis, Autophagy and Energetic Impairment in Bladder Cancer

Quantitative MALDI Imaging of Spatial Distributions and Dynamic Changes of Tetrandrine in Multiple Organs of Rats

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