Evaluation of ellagic acid as an inhibitor of sphingosine kinase 1: A targeted approach towards anticancer therapy

Gupta, Preeti; Mohammad, Taj; Κhan, Parvez; Alajmi, Mohamed F.; Hussain, Afzal; Rehman, Tabish; Hassan, Md. Imtaiyaz

doi:10.1016/j.biopha.2019.109245

Cited by 84 publications

(35 citation statements)

References 61 publications

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“…In addition, EA was reported to inhibit tau phosphorylation, one of the prime suspects involved in AD pathology, leading to learning and memory improvements in a mice model of AD [ 50 ]. In a more recent study, EA revealed a strong binding affinity for sphingosine kinase 1, repressing phosphorylation by restricting ATP accessibility [ 51 ]. However, the evidence of such phospho-inhibitory potential does not explain the observed repression of NFAT activation, nor the increase in IL-10.…”

Section: Discussionmentioning

confidence: 99%

Bioaccessible Raspberry Extracts Enriched in Ellagitannins and Ellagic Acid Derivatives Have Anti-Neuroinflammatory Properties

et al. 2020

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Chronic neuroinflammation associated with neurodegenerative disorders has been reported to be prevented by dietary components. Particularly, dietary (poly)phenols have been identified as having anti-inflammatory and neuroprotective actions, and their ingestion is considered a major preventive factor for such disorders. To assess the relation between (poly)phenol classes and their bioactivity, we used five different raspberry genotypes, which were markedly different in their (poly)phenol profiles within a similar matrix. In addition, gastro-intestinal bio-accessible fractions were produced, which simulate the (poly)phenol metabolites that may be absorbed after digestion, and evaluated for anti-inflammatory potential using LPS-stimulated microglia. Interestingly, the fraction from genotype 2J19 enriched in ellagitannins, their degradation products and ellagic acid, attenuated pro-inflammatory markers and mediators CD40, NO, TNF-α, and intracellular superoxide via NF-κB, MAPK and NFAT pathways. Importantly, it also increased the release of the anti-inflammatory cytokine IL-10. These effects contrasted with fractions richer in anthocyanins, suggesting that ellagitannins and its derivatives are major anti-inflammatory (poly)phenols and promising compounds to alleviate neuroinflammation

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Section: Discussionmentioning

confidence: 99%

Bioaccessible Raspberry Extracts Enriched in Ellagitannins and Ellagic Acid Derivatives Have Anti-Neuroinflammatory Properties

et al. 2020

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“…Nonetheless, today the growing interest in these compounds is mainly associated with the consumption and development of new products offering beneficial health effects linked to phenolic antioxidant properties [ 5 ]. Accordingly, owing to beneficial health effects against many oxidative-linked chronic diseases, including cancer and neurodegenerative diseases, EA has generated a noticeable scientific interest [ 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. Beyond food and biomedical applications, EA and ET’s scientific relevance can be linked to advanced materials such as copolymers [ 14 ], chelating reagents [ 15 ], ion-exchange resins [ 16 ], and materials for electrochemical devices [ 17 ], among others.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances in the Production and Applications of Ellagic Acid and Its Derivatives. A Review

2020

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Ellagitannins (ETs), characterized by their diversity and chemical complexity, belong to the class of hydrolysable tannins that, via hydrolysis under acidic or alkaline conditions, can yield ellagic acid (EA). They are mostly found as a part of extractives in angiosperms. As known antioxidants and chelators, EA and EA derivatives are drawing an increasing interest towards extensive technical and biomedical applications. The latter ones include possible antibacterial, antifungal, antiviral, anti-inflammatory, hepato- and cardioprotective, chemopreventive, neuroprotective, anti-diabetic, gastroprotective, antihyperlipidemic, and antidepressant-like activities, among others. EA’s synthesis and production challenges prompt further research on new methods and alternative sources. Conventional and prospective methods and raw materials for the production of EA and its derivatives are reviewed. Among the potential sources of EA, the residues and industrial streams of the pulp industry have been highlighted and considered as an alluring alternative in terms of commercial exploitation.

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“…To further evaluate the inhibitory potential and to calculate the IC 50 values of the compounds’ hits revealed from initial screening, an enzymatic assay of SphK1 was performed across a narrower range (0–35 μM). The ATPase activity of SphK1 was quantified in terms of hydrolyzed phosphate in picomolar concentration using a phosphate standard curve as described [ 62 , 63 ]. The decrease in the activity of SphK1 was plotted in terms of percentage inhibition against an increasing dose of respective compounds, which revealed IC 50 values in the micromolar range ( Figure 7 , Table 3 ).…”

Section: Resultsmentioning

confidence: 99%

“…The reaction containing no protein was set up to obtain the background reading of inorganic phosphate. The inhibition of SphK1 activity was plotted in terms of percentage using a standard phosphate curve as described [62,78]. The data points were calculated from three independent experiments in triplicate.…”

Section: Enzyme Inhibition Assaymentioning

confidence: 99%

Design and Development of Novel Urea, Sulfonyltriurea, and Sulfonamide Derivatives as Potential Inhibitors of Sphingosine Kinase 1

et al. 2020

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Sphingosine kinase 1 (SphK1) is one of the well-studied drug targets for cancer and inflammatory diseases. Recently discovered small-molecule inhibitors of SphK1 have been recommended in cancer therapeutics; however, selectivity and potency of first-generation inhibitors are great challenge. In search of effective SphK1 inhibitors, a set of small molecules have been designed and synthesized bearing urea, sulfonylurea, sulfonamide, and sulfonyltriurea groups. The binding affinity of these inhibitors was measured by fluorescence-binding assay and isothermal titration calorimetry. Compounds 1, 5, 6, and 7 showed an admirable binding affinity to the SphK1 in the sub-micromolar range and significantly inhibited SphK1 activity with admirable IC50 values. Molecular docking studies revealed that these compounds fit well into the sphingosine binding pocket of SphK1 and formed significant number of hydrogen bonds and van der Waals interactions. These molecules may be exploited as potent and selective inhibitors of SphK1 that could be implicated in cancer therapeutics after the required in vivo validation.

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Evaluation of ellagic acid as an inhibitor of sphingosine kinase 1: A targeted approach towards anticancer therapy

Cited by 84 publications

References 61 publications

Bioaccessible Raspberry Extracts Enriched in Ellagitannins and Ellagic Acid Derivatives Have Anti-Neuroinflammatory Properties

Bioaccessible Raspberry Extracts Enriched in Ellagitannins and Ellagic Acid Derivatives Have Anti-Neuroinflammatory Properties

Recent Advances in the Production and Applications of Ellagic Acid and Its Derivatives. A Review

Design and Development of Novel Urea, Sulfonyltriurea, and Sulfonamide Derivatives as Potential Inhibitors of Sphingosine Kinase 1

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