STAT3 inhibitory activity of naphthoquinones isolated from Tabebuia avellanedae

Tahara, Teruyuki; Watanabe, Ami; Yutani, Maho; Yamano, Yuko; Sagara, Mami; Nagai, Shizu; Saito, Keita; Yamashita, Mitsuaki; Ihara, Makoto; Iida, Akira

doi:10.1016/j.bmc.2020.115347

Cited by 19 publications

(19 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The 3D structure of Cpd9 and Cpd19 were obtained by Gaussian View [ 29 ] and then optimized with Gaussian 09 software [ 29 ] at B3LYP 6-31G* set [ 30 ]. Then, Cpd9 and Cpd19 were docked to BRD4 with AutoDock 4.2.6 software [ 31 ]. The Lamarckian genetic algorithm was used to predict the stereo conformation and select the lowest energy system for further MD.…”

Section: Methodsmentioning

confidence: 99%

Molecular Dynamic Simulations of Bromodomain and Extra-Terminal Protein 4 Bonded to Potent Inhibitors

Chen

Geng

et al. 2021

Molecules

View full text Add to dashboard Cite

Bromodomain and extra-terminal domain (BET) subfamily is the most studied subfamily of bromodomain-containing proteins (BCPs) family which can modulate acetylation signal transduction and produce diverse physiological functions. Thus, the BET family can be treated as an alternative strategy for targeting androgen-receptor (AR)-driven cancers. In order to explore the effect of inhibitors binding to BRD4 (the most studied member of BET family), four 150 ns molecular dynamic simulations were performed (free BRD4, Cpd4-BRD4, Cpd9-BRD4 and Cpd19-BRD4). Docking studies showed that Cpd9 and Cpd19 were located at the active pocket, as well as Cpd4. Molecular dynamics (MD) simulations indicated that only Cpd19 binding to BRD4 can induce residue Trp81-Ala89 partly become α-helix during MD simulations. MM-GBSA calculations suggested that Cpd19 had the best binding effect with BRD4 followed by Cpd4 and Cpd9. Computational alanine scanning results indicated that mutations in Phe83 made the greatest effects in Cpd9-BRD4 and Cpd19-BRD4 complexes, showing that Phe83 may play crucial roles in Cpd9 and Cpd19 binding to BRD4. Our results can provide some useful clues for further BCPs family search.

show abstract

Section: Methodsmentioning

confidence: 99%

Molecular Dynamic Simulations of Bromodomain and Extra-Terminal Protein 4 Bonded to Potent Inhibitors

Chen

Geng

et al. 2021

Molecules

View full text Add to dashboard Cite

show abstract

“…They observed that T. avellanedae administration prolonged the lifespan of tumor-bearing mice by increasing the number of bone marrow granulocyte-macrophage colony-forming units and reducing colony-stimulating activity levels; the optimal biologically active dose was 120 mg/kg. In addition, Tahara et al [ 14 ] found that naphthoquinones isolated from T. avellanedae markedly blocked the STAT3 pathway while reducing hyperactivation of these signals as well as inhibited growth of cancer cell lines.…”

Section: Pharmacological Activitiesmentioning

confidence: 99%

“…In recent years, along with thorough research, some of the principal active components of T. impetiginosa have been used in clinical research. For example, β-lapachone, mainly distributed in heartwood of T. impetiginosa, has entered into phase 2 clinical trials for treatment of squamous cell carcinoma, and 2-acetylnaphtho (2,3-β) furan-4,9-dione, also referred to as STAT3 inhibitor BBI608 (Napabucacin), was developed by Boston Biomedical Inc [ 14 ].…”

Section: Clinical Trialsmentioning

confidence: 99%

“…Several categories of compounds have been isolated and identified from T. impetiginosa, principally quinones, flavonoids, naphthoquinones, and benzoic acids [ 9 , 10 , 11 , 12 ]. In recent years, many investigations have demonstrated that extracts or compounds isolated from T. impetiginosa reveal an extensive range of pharmacological activities such as anti-obesity, antifungal, anti-psoriatic, antioxidant, anti-inflammatory, and anti-cancer activities [ 4 , 7 , 13 , 14 , 15 , 16 , 17 , 18 ]. It is particularly prominent in immunopharmacology.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Tabebuia impetiginosa: A Comprehensive Review on Traditional Uses, Phytochemistry, and Immunopharmacological Properties

et al. 2020

View full text Add to dashboard Cite

Tabebuia impetiginosa, a plant native to the Amazon rainforest and other parts of Latin America, is traditionally used for treating fever, malaria, bacterial and fungal infections, and skin diseases. Additionally, several categories of phytochemicals and extracts isolated from T. impetiginosa have been studied via various models and displayed pharmacological activities. This review aims to uncover and summarize the research concerning T. impetiginosa, particularly its traditional uses, phytochemistry, and immunopharmacological activity, as well as to provide guidance for future research. A comprehensive search of the published literature was conducted to locate original publications pertaining to T. impetiginosa up to June 2020. The main inquiry used the following keywords in various combinations in titles and abstracts: T. impetiginosa, Taheebo, traditional uses, phytochemistry, immunopharmacological, anti-inflammatory activity. Immunopharmacological activity described in this paper includes its anti-inflammatory, anti-allergic, anti-autoimmune, and anti-cancer properties. Particularly, T. impetiginosa has a strong effect on anti-inflammatory activity. This paper also describes the target pathway underlying how T. impetiginosa inhibits the inflammatory response. The need for further investigation to identify other pharmacological activities as well as the exact target proteins of T. impetiginosa was also highlighted. T. impetiginosa may provide a new strategy for prevention and treatment of many immunological disorders that foster extensive research to identify potential anti-inflammatory and immunomodulatory compounds and fractions as well as to explore the underlying mechanisms of this herb. Further scientific evidence is required for clinical trials on its immunopharmacological effects and safety.

show abstract

“…Cytokines or growth factors interact with their cell surface receptors and recruit STAT3, which causes STAT3 phosphorylation at Tyr705 by JAK and other kinases. , The phosphorylated STAT3 (pSTAT3) further forms a homodimer through interactions between Tyr705 of the SH2 domain. The dimeric pSTAT3 then translocates to the nucleus and acts as a transcription factor by up-regulating the expression of genes that are critical for the survival and proliferation of cancer cells. − Several plant-derived small molecules have been reported to inhibit the STAT3 signaling pathway by directly binding to the key residues of the SH2 domain. ,, …”

mentioning

confidence: 99%

Aspeterreurone A, a Cytotoxic Dihydrobenzofuran–Phenyl Acrylate Hybrid from the Deep-Sea-Derived Fungus Aspergillus terreus CC-S06-18

et al. 2020

View full text Add to dashboard Cite

A new dihydrobenzofuran–phenyl acrylate hybrid, aspeterreurone A (1), was obtained from the culture of the deep-sea-derived fungus Aspergillus terreus CC-S06-18. The relative configuration of 1 was elucidated by HSQMBC NMR, calculated NMR chemical shifts coupled with a statistical procedure (DP4+), and the absolute configuration was established by ECD calculations. 1 exhibited cytotoxicities against the gastric cancer cell lines HGC27, MGC803, BGC823, and AGS, with minimal effects on normal gastric epithelial cell line GES-1. Further studies showed that 1 inhibited cell cycle progression and induced apoptosis of gastric cancer MGC803 cells in a concentration-dependent manner. Western blot analysis indicated that 1 inhibited the phosphorylation of STAT3, which might contribute to its cytotoxic activity.

show abstract

STAT3 inhibitory activity of naphthoquinones isolated from Tabebuia avellanedae

Cited by 19 publications

References 30 publications

Molecular Dynamic Simulations of Bromodomain and Extra-Terminal Protein 4 Bonded to Potent Inhibitors

Molecular Dynamic Simulations of Bromodomain and Extra-Terminal Protein 4 Bonded to Potent Inhibitors

Tabebuia impetiginosa: A Comprehensive Review on Traditional Uses, Phytochemistry, and Immunopharmacological Properties

Aspeterreurone A, a Cytotoxic Dihydrobenzofuran–Phenyl Acrylate Hybrid from the Deep-Sea-Derived Fungus Aspergillus terreus CC-S06-18

Contact Info

Product

Resources

About