Reynoutria Japonica from Traditional Chinese Medicine: A Source of Competitive Adenosine Deaminase Inhibitors for Anticancer

Zhang, Xinguo; Ma, Guo-Yan; Kou, Fei; Liu, Wenjie; Sun, Qiao-Yun; Guangjun, Guo; Ma, Xiangyuan; Guo, Si-Jia; Zhu, Jun

doi:10.2174/1386207322666190415100618

Cited by 12 publications

(8 citation statements)

References 48 publications

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“…To compare the in-silico theoretical study with practical data, the ADA enzyme was isolated from rat joints and assayed in the absence and presence of Fenugreek QUE. The ADA activity was inhibited in rat joints by Fenugreek QUE with an IC 50 value of 0.17 mM, whereas previous study reported that the IC 50 value of Reynoutria japonica which represented a natural inhibitor of ADA was 0.629 mM (Zhang et al 2019 ). The fenugreek QUE acts as a non-competitive inhibitor with a K i value of 55.5 mM.…”

Section: Discussionmentioning

confidence: 87%

Quercetin mitigates rheumatoid arthritis by inhibiting adenosine deaminase in rats

El-Said

Atta

Mobasher

et al. 2022

Mol Med

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Rheumatoid arthritis (RA) is a chronic inflammatory joint disease characterized by synovial proliferation and bone destruction. Adenosine deaminase (ADA) is a key inflammatory enzyme that increases joint stiffness and pain in RA. In this study, we evaluated the in-silico, and in vivo inhibitory effect of quercetin isolated from Egyptian Fenugreek on ADA enzyme activity. We also determined the combinatorial effect of quercetin on methotrexate mediated anti-inflammatory efficacy and toxicity. In-silico molecular docking was conducted and confirmed in an in vivo RA rat model. The results showed that the inhibition constant of quercetin on joint ADA by docking and in-vitro was 61.9 and 55.5 mM, respectively. Therefore, quercetin exhibits anti-inflammatory effect in a rat RA model as evidenced by reducing the specific activity of ADA in joint tissues, lower jaw volume, enhance body weight, downregulate ADA gene expression, reduce levels of RA cytokines interleukin-1β, interleukin-6, tumor necrosis factor-α, also, rheumatoid factor, C-reactive protein, and anti-cyclic citrullinated peptide RA biomarker levels. These findings demonstrate that the purified quercetin has a promising anti-inflammatory effect against RA disease through its inhibitory effects on the ADA enzyme. Furthermore, isolated quercetin improved the anti-inflammatory efficacy of methotrexate, reduced its toxic effects by increasing antioxidant enzymes and reducing oxidative stress.

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Section: Discussionmentioning

confidence: 87%

Quercetin mitigates rheumatoid arthritis by inhibiting adenosine deaminase in rats

El-Said

Atta

Mobasher

et al. 2022

Mol Med

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“…Molecular docking analysis showed that emodin could bind to the active site of ADA tightly, which significantly protected cordycepin against degradation. The cytotoxic activity of cordycepin against leukemia K562 cells was strongly enhanced in combination with emodin in vitro (Zhang et al, 2019).…”

Section: Methods For Improving the Bioavailability And Efficacy Of Co...mentioning

confidence: 99%

Cordycepin: A review of strategies to improve the bioavailability and efficacy

Chen

Luo

Jiang

et al. 2023

Phytotherapy Research

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Cordycepin is a bioactive compound extracted from Cordyceps militaris. As a natural antibiotic, cordycepin has a wide variety of pharmacological effects. Unfortunately, this highly effective natural antibiotic is proved to undergo rapid deamination by adenosine deaminase (ADA) in vivo and, as a consequence, its half‐life is shortened and bioavailability is decreased. Therefore, it is of critical importance to work out ways to slow down the deamination so as to increase its bioavailability and efficacy. This study reviews recent researches on a series of aspects of cordycepin such as the bioactive molecule's pharmacological action, metabolism and transformation as well as the underlying mechanism, pharmacokinetics and, particularly, the methods for reducing the degradation to improve the bioavailability and efficacy. It is drawn that there are three methods that can be applied to improve the bioavailability and efficacy: to co‐administrate an ADA inhibitor and cordycepin, to develop more effective derivatives via structural modification, and to apply new drug delivery systems. The new knowledge can help optimize the application of the highly potent natural antibiotic‐cordycepin and develop novel therapeutic strategies.

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“…The H-bond length between the ligand and protein residues was found to be in the range of 1.65 to 2.92 Å. Adenosine kinase inhibitors are known to possess anti-inflammatory, antinociceptive, and anticonvulsant activity in animal models. Recent reports on AK inhibitors suggest that the modification of the Adenosine kinase-mediated pathway has a potential role in cancer therapy [27][28][29]. GSK-3β plays a significant role in neurodegenerative diseases and diabetes, and has been investigated for the anticancer disease treatment strategies as well, where it has produced fruitful results [30][31][32].…”

Section: Molecular Dockingmentioning

confidence: 99%

1,5-Benzothiazepine Derivatives: Green Synthesis, In Silico and In Vitro Evaluation as Anticancer Agents

et al. 2022

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Considering the importance of benzothiazepine pharmacophore, an attempt was carried out to synthesize novel 1,5-benzothiazepine derivatives using polyethylene glycol−400 (PEG−400)-mediated pathways. Initially, different chalcones were synthesized and then subjected to a cyclization step with benzothiazepine in the presence of bleaching clay and PEG−400. PEG−400-mediated synthesis resulted in a yield of more than 95% in less than an hour of reaction time. Synthesized compounds 2a−2j were investigated for their in vitro cytotoxic activity. Moreover, the same compounds were subjected to systematic in silico screening for the identification of target proteins such as human adenosine kinase, glycogen synthase kinase−3β, and human mitogen-activated protein kinase 1. The compounds showed promising results in cytotoxicity assays; among the tested compounds, 2c showed the most potent cytotoxic activity in the liver cancer cell line Hep G−2, with an IC50 of 3.29 ± 0.15 µM, whereas the standard drug IC50 was 4.68 ± 0.17 µM. In the prostate cancer cell line DU−145, the compounds displayed IC50 ranges of 15.42 ± 0.16 to 41.34 ± 0.12 µM, while the standard drug had an IC50 of 21.96 ± 0.15 µM. In terms of structural insights, the halogenated phenyl substitution on the second position of benzothiazepine was found to significantly improve the biological activity. This characteristic feature is supported by the binding patterns on the selected target proteins in docking simulations. In this study, 1,5-benzothiazepines have been identified as potential anticancer agents which can be further exploited for the development of more potent derivatives.

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Reynoutria Japonica from Traditional Chinese Medicine: A Source of Competitive Adenosine Deaminase Inhibitors for Anticancer

Cited by 12 publications

References 48 publications

Quercetin mitigates rheumatoid arthritis by inhibiting adenosine deaminase in rats

Quercetin mitigates rheumatoid arthritis by inhibiting adenosine deaminase in rats

Cordycepin: A review of strategies to improve the bioavailability and efficacy

1,5-Benzothiazepine Derivatives: Green Synthesis, In Silico and In Vitro Evaluation as Anticancer Agents

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