&lt;i&gt;In Vitro&lt;/i&gt; Characterization of Derrone as an Aurora Kinase Inhibitor

Nhung, Hoang Thi My; Phuong, Thuong Thien; Nguyen, Ty; Tran, Thi Hai Yen; Nguyen, Anh Thi Ngoc; Nguyen, Thanh Lai; Bui, Khanh Thi Van

doi:10.1248/bpb.b15-00835

Cited by 13 publications

(16 citation statements)

References 41 publications

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“…For example, AKI-001 [100], BPR1K871 [89], CCT137690 [97,98], JNJ-7706621 [92], SAR156497 [93], SCH-1473759 [90] and VE-465 [95] have potent inhibitory effects on Aurora kinase activity with IC50 values< 50 nM. Other Aurora kinase inhibitors with IC50 values> 50 nM against kinase activity, such as BPR1K653 [87], CCT129202 [96], derrone [91], PHA-680632 [99], R1498 [94], reversine [101] and TY-011 [88], have also been tested in preclinical studies, and the preliminary data are shown in Table 3. U14 cell xenograft; mice were treated with reversine (10 mg/kg) alone or with aspirin (1 μg/kg), i.p per 3 days; tumor growth was reduced and the mice survived longer in the combination group.…”

Section: Pan Aurora Kinase Inhibitorsmentioning

confidence: 99%

“…Researchers can take advantage of the high-resolution 3D protein structures and computer docking tools to find natural compound or FDA approved drugs that target AURKA. For example, derrone, extracted from erythrina orientalis, is screened from 100 natural substances to inhibit AURKA kinase activity and cell growth [91]. Another case is bioactive tanshinone I which is from traditional Chinese herbal medicine Salvia miltiorrhiza.…”

Section: Conclusion and Outlooksmentioning

confidence: 99%

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Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy

et al. 2021

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Aurora kinase A (AURKA) belongs to the family of serine/threonine kinases, whose activation is necessary for cell division processes via regulation of mitosis. AURKA shows significantly higher expression in cancer tissues than in normal control tissues for multiple tumor types according to the TCGA database. Activation of AURKA has been demonstrated to play an important role in a wide range of cancers, and numerous AURKA substrates have been identified. AURKA-mediated phosphorylation can regulate the functions of AURKA substrates, some of which are mitosis regulators, tumor suppressors or oncogenes. In addition, enrichment of AURKA-interacting proteins with KEGG pathway and GO analysis have demonstrated that these proteins are involved in classic oncogenic pathways. All of this evidence favors the idea of AURKA as a target for cancer therapy, and some small molecules targeting AURKA have been discovered. These AURKA inhibitors (AKIs) have been tested in preclinical studies, and some of them have been subjected to clinical trials as monotherapies or in combination with classic chemotherapy or other targeted therapies.

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Section: Pan Aurora Kinase Inhibitorsmentioning

confidence: 99%

Section: Conclusion and Outlooksmentioning

confidence: 99%

Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy

et al. 2021

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“…The tumor growth of MCF‐7 spheroids decreased in the presence of derrone. After 15 days of treatment, tumor spheroid growth inhibition (%TGI) was 17.5% and 65.4% for 30 and 60 µM, respectively (Hoang et al., 2016).…”

Section: Akis Of Natural Originmentioning

confidence: 99%

Design strategies, SAR, and mechanistic insight of Aurora kinase inhibitors in cancer

2021

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Aurora kinases (AURKs) are serine/threonine protein kinases that play a critical role during cell proliferation. Three isoforms of AURKs reported in mammals include AURKA, AURKB, AURKC, and all share a similar C‐terminal catalytic domain with differences in their subcellular location, substrate specificity, and function. Recent research reports indicate an elevated expression of these kinases in several cancer types highlighting their role as oncogenes in tumorigenesis. Inhibition of AURKs is an attractive strategy to design potent inhibitors modulating this target. The last few years have witnessed immense research in the development of AURK inhibitors with few FDA approvals. The current clinical therapeutic regime in cancer is associated with severe side‐effects and emerging resistance to existing drugs. This has been the key driver of research initiatives toward designing more potent drugs that can potentially circumvent the emerging resistance. This review is a comprehensive summary of recent research on AURK inhibitors and presents the development of scaffolds, their synthetic schemes, structure–activity relationships, biological activity, and enzyme inhibition potential. We hope to provide the reader with an array of scaffolds that can be selected for further research work and mechanistic studies in the development of new AURK inhibitors.

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“…Some closed effects can also be observed with respect to AIF in lung cancer and leukemia cells (see above). Nonetheless, its cellular effects are also ascribed to its strong inhibitory effects against Aurora kinases A and B, with the respective IC 50 of 22.3 µM and 6 µM in direct kinase inhibition assays [ 50 ]. Aurora kinases are essential serine/threonine kinase proteins, used during mitosis via their key roles in chromosomal segregation and cell polyploidy [ 50 ].…”

Section: In Vitro Anticancerous Activities Of Compounds From E Senegalensis : Mechanisms Of Actionmentioning

confidence: 99%

“…Nonetheless, its cellular effects are also ascribed to its strong inhibitory effects against Aurora kinases A and B, with the respective IC 50 of 22.3 µM and 6 µM in direct kinase inhibition assays [ 50 ]. Aurora kinases are essential serine/threonine kinase proteins, used during mitosis via their key roles in chromosomal segregation and cell polyploidy [ 50 ]. Their overexpression in many cancers including colon, breast, prostate, pancreatic and thyroid cancer is associated with advanced stages and poor prognosis [ 77 ].…”

Section: In Vitro Anticancerous Activities Of Compounds From E Senegalensis : Mechanisms Of Actionmentioning

confidence: 99%

Systematic Review of Potential Anticancerous Activities of Erythrina senegalensis DC (Fabaceae)

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Ouédraogo

Esposito

et al. 2021

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The objective of this study was to carry out a systematic review of the substances isolated from the African medicinal plant Erythrina senegalensis, focusing on compounds harboring activities against cancer models detailed in depth herein at both in vitro and in vivo preclinical levels. The review was conducted through Pubmed and Google Scholar. Nineteen out of the forty-two secondary metabolites isolated to date from E. senegalensis displayed interesting in vitro and/or in vivo antitumor activities. They belonged to alkaloid (Erysodine), triterpenes (Erythrodiol, maniladiol, oleanolic acid), prenylated isoflavonoids (senegalensin, erysenegalensein E, erysenegalensein M, alpinumisoflavone, derrone, warangalone), flavonoids (erythrisenegalone, senegalensein, lupinifolin, carpachromene) and pterocarpans (erybraedine A, erybraedine C, phaseollin). Among the isoflavonoids called “erysenegalensein”, only erysenealenseins E and M have been tested for their anticancerous properties and turned out to be cytotoxic. Although the stem bark is the most frequently used part of the plant, all pterocarpans were isolated from roots and all alkaloids from seeds. The mechanisms of action of its metabolites include apoptosis, pyroptosis, autophagy and mitophagy via the modulation of cytoplasmic proteins, miRNA and enzymes involved in critical pathways deregulated in cancer. Alpinumisoflavone and oleanolic acid were studied in a broad spectrum of cancer models both in vitro and in preclinical models in vivo with promising results. Other metabolites, including carpachromen, phaseollin, erybraedin A, erysenegalensein M and maniladiol need to be further investigated, as they display potent in vitro effects.

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<i>In Vitro</i> Characterization of Derrone as an Aurora Kinase Inhibitor

Cited by 13 publications

References 41 publications

Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy

Targeting AURKA in Cancer: molecular mechanisms and opportunities for Cancer therapy

Design strategies, SAR, and mechanistic insight of Aurora kinase inhibitors in cancer

Systematic Review of Potential Anticancerous Activities of Erythrina senegalensis DC (Fabaceae)

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